Maggie Pierce must step up to the plate as the new cardiothoracic surgeon after the departure of Cristina, and clashes with Meredith in the OR. Callie and Arizona debate over the use of a surrogate, with Callie being skeptical about it but later changes her mind. Arizona is given an opportunity from Dr. Herman to become a fetal surgery fellow, which she accepts. Alex and Bailey fight for Cristina's position on the board. Meanwhile, Richard, Jackson, and Derek try to distract Owen from Cristina's departure by inviting him to hang out. Jo becomes jealous after Meredith and Alex's relationship becomes closer after the departure of Cristina. After fighting over Meredith's decision, Derek tells Meredith that he chooses her and the kids over his brain mapping initiative in Washington, D.C.

Maggie tries to get used to Grey Sloan Memorial Hospital, and learns the difficulty of connecting with others. Jo, trying to win over Maggie, tells her about Alex's dilemma involving Dr. Oliver Lebackes' private practice and his seat on the board, which Maggie talks about during surgery with the two, which results in Alex being fired from the private practice. Maggie finds herself beginning a friendship with Amelia and finds out that Meredith is not so bad to know. She expresses interest in Bailey's genome mapping project, and she uses it and Cristina's research with the McNeil family to solve their family's case. After an extended argument, Callie decides that Arizona should do the fetal surgery fellowship and that they would work it out with having a second child. After her conversation with Amelia, Maggie tells Meredith that Ellis Grey is her mother, too. Meredith does not believe her and becomes furious with Maggie.

Owen takes Callie to a veteran's hospital with hopes of her using her lab to provide wounded veterans with robotic legs. However, damaged nerves in the veteran's legs becomes a problem, but Jackson manages to fix it. As Alex tries to prepare for his presentation to fill Cristina's position on the board, Meredith distracts him with the news of her new half-sister, Maggie. They discover that Maggie is indeed Meredith's half-sister. Derek and Amelia fight over being the Chief of Neurosurgery, which makes Derek second guess his decision to stay in Seattle. With the new fellowship and the wounded veterans project, Arizona and Callie doubt their future together. Richard attempts to tell Maggie that he is her father, but she reveals that she'd already known about it and is furious that he didn't tell her sooner. Alex and Bailey go head to head in front of the board for the open spot, with Bailey being given the seat.

In a series of flashbacks, Meredith and Richard manage to come to terms with their past relationships with Ellis. Meredith goes searching through her mother's diaries and video footage in order to learn more about her half-sister. Alex learns that the board's vote was unanimously in favor of Bailey. When he confronts Arizona about it, she instead hires him as the new pediatrics attending so she can focus on the fetal surgery fellowship. Meredith and Derek's fight over D.C. subsides once Maggie tells Derek she is Meredith's half-sister. Bailey finds out from Richard who Maggie really is after learning why Maggie wants to leave the hospital. Meredith learns that the day at the carousel was the day Richard left Ellis for good, after being jealous of Ellis for the Harper Avery award. Meredith manages to remember Ellis' pregnancy and has a change of heart about Maggie.

Absent: Sarah Drew as April Kepner.

Callie and Arizona find themselves in marriage counseling where the counselor suggests a 30-day separation with the rules of no talking or sexual activity. During their separation, Arizona is granted more time to focus on her fellowship and sharpen her fetal surgery skills; however, she messes up one too many times which upsets Dr. Herman. Alex also becomes angry at Arizona after going against his decision on a case. Meanwhile, Callie becomes closer to Meredith as they both are having marital problems. After a successful 30 day separation, Arizona expresses her love to Callie and says she needs her. Callie does not reciprocate and says that she felt free during the separation and needs more time to love herself.

Absent: Chandra Wilson as Miranda Bailey

Jo becomes emotional after performing surgery on a homeless veteran that was living in her car, which makes her realize her progression with Alex. Bailey learns a lesson about her health after one of her patients dies from cancer to the esophagus after not taking good care of himself. April's mother, Karen, arrives in Seattle to help April and Jackson prepare the nursery for their baby, which creates tension with April but she later forgives her mother for the unwelcome surprise. Derek invites Maggie and Richard to dinner, despite Meredith's pleas to cancel. When they forget the time, Maggie and Richard have a conversation outside the house where Richard apologizes for his behavior. Arizona learns that Dr. Herman has an inoperable brain tumor, with only six months to live, and Dr. Herman wants to teach her a year of medicine in six months.

Absent: Caterina Scorsone as Amelia Shepherd.

Amelia's secret about being a drug addict is revealed at the hospital when a patient's daughter, who knows about Amelia's past, demands another doctor once she finds out that Amelia is her surgeon. Amelia seeks comfort and advice from Richard. Owen asks Derek for help when Amelia refuses to discuss her past with him. Derek accidentally leads Owen to believe that Amelia is not sober, but Derek later tells the truth. He confesses to Amelia to have hit rock bottom after trying to do right by his wife, kids, and her. Arizona takes on a case without Dr. Herman, and is able to save the baby, but the mother dies on the table. Dr. Herman later shows up, admitting to have gotten a dose of radiation treatment. After assisting Arizona in surgery, April becomes more concerned about her own pregnancy. Bailey teaches Jo a lesson after Jo is unable to remember every step of her first solo surgery.

Arizona becomes more concerned about Dr. Herman after she begins to show symptoms during surgery. Arizona gets a hold of Dr. Herman's scans, which she shows to Amelia, who tells Arizona that she can save Dr. Herman's life. Callie and Owen's work with robotic limbs is paused after one of the patients hits his head during training and find himself in a coma. Stephanie detects a possible life-threatening birth defect for April and Jackson's baby on an ultrasound, which Dr. Herman later confirms. Derek is again offered the job in D.C. by the POTUS, and the situation intensifies his fight with Meredith. Meredith, tired of Derek's excuses for turning down the job, tells him to take the job which Derek does.

Multiple car accidents caused by a woman with insulinoma brings patients to the ER. April and Jackson deal with the news that their unborn baby boy has osteogenesis imperfecta, a life threatening disease with little hope. Meredith must cope with the absence of Derek who took off to Washington, D.C., but Meredith and Derek decide that Derek should go through with his trip, and that they will make it work. Arizona and Amelia study Dr. Herman's tumor, and they come up with a game plan. At first, Dr. Herman is pessimistic and thinks there is no hope. However, she finally succumbs to Arizona's optimistic point-of-view and agrees to go forth with the surgery only once it becomes almost inoperable.

Meredith feels more alone than ever after both Derek and Cristina have left her. Amelia begins to question her plan for removing Dr. Herman's tumor and begins to think that she will fail, but her hope restores after a talk with Richard. April and Jackson continue to struggle with their situation, with discussing what to do if their baby has Type II of osteogenesis imperfecta. Jackson wants an abortion if it is Type II, but it goes against April's Christian beliefs. Callie and Owen meet with a sales representative to discuss parts for their robotic limbs lab. Later at Joe's, Callie declines a one-night stand with the sale representative. Meredith, Maggie, and Bailey team up to perform surgery on a woman who has a difficult tumor in her abdomen, and they successfully remove the tumor after 3-D printing scans of it.

Absent: Patrick Dempsey as Derek Shepherd

After receiving news about their baby having Type II osteogenesis imperfecta, April begins to doubt her beliefs in a just and loving God. Catherine Avery arrives at Grey Sloan Memorial to comfort her son and daughter-in-law and suggests that they set a date to induce labor, baptize him, and love him until God takes him. At first, April and Jackson go along with the idea, but later begin to have their doubts. Callie and Bailey help save the life of a woman who was accidentally shot by her husband and gives birth to a child she was unaware of. Maggie offers herself to babysit Meredith's kids so Meredith can visit Derek. Amelia continues to work with Stephanie on Dr. Herman's tumor case and test their plan on a patient with a similar tumor. April has a conversation with a woman who lost her fiancé in a car wreck, and after the conversation, April finds the strength to induce and have her son, whom she names Samuel Norbert Avery.

Absent: Patrick Dempsey as Derek Shepherd

Meredith is evasive when asked about her weekend in Washington DC with Derek. Bailey goes with Ben and his brother to the woods to scatter their father's ashes, but the brother faints and falls. At the hospital Bailey and Meredith find out that Ben's brother is transitioning to be a woman, which upsets Ben. A patient pretends to faint in order to deflect a proposal by her boyfriend, but Callie tells the boyfriend the truth after the woman pretends to faint again at the hospital. Richard feels used by Catherine, Callie reenters the dating scene, and Owen and Amelia kiss for the first time. Maggie becomes suspicious of Meredith about her whereabouts over the weekend after she was called by Derek multiple times. Meredith tells Alex the truth that she stayed at a hotel alone for the entire weekend, just enjoying being alone.

Absent: Patrick Dempsey as Derek Shepherd and Sarah Drew as April Kepner due to maternity leave.

In the weeks leading up to Dr. Herman's surgery, Dr. Herman and Arizona attack the board of surgeries they have planned before she dies. Bailey has a special request, as the wife of her ex-patient is now pregnant with the baby having a tumor; however Dr. Herman declines. Amelia begins to lecture about her plan for removing Dr. Herman's tumor, with more and more doctors attending the conference. However, at the same time, Amelia begins to doubt herself, believing herself to not be better than Derek. After weeks of radiation therapy, Dr. Herman's tumor finally invades the optic chiasm, rendering her visually impaired, leading Amelia to schedule surgery for that day. Glenda Castillo, Bailey's patient, is sent to emergency surgery with Arizona prepping to operate her first solo fetal surgery.

Absent: Patrick Dempsey as Derek Shepherd, Sarah Drew as April Kepner due to maternity leave, and Jesse Williams as Jackson Avery.

Dr. Herman's surgery begins, at the same time as Arizona and Bailey trying to save the life of Glenda Castillo. They have different opinions on how to proceed with the surgery, with Bailey wanting to deliver the baby while Arizona wants to keep the baby inside. At Dr. Herman's surgery, Amelia begs Richard to call Derek as she claims to be unable to continue. However, Richard comes up with encouraging advice, leading Amelia to proceed. Arizona, after some obstacles from Bailey, is able to save the patient and her baby. Amelia manages to remove the tumor, but after several days, Dr. Herman still does not wake up. Stephanie figures out that Dr. Herman had a small stroke, but luckily Dr. Herman eventually wakes up, but is completely blind. Amelia instructs Stephanie to live on the high and not beat herself up.

Absent: Patrick Dempsey as Derek Shepherd

An earthquake strikes Seattle, sending a flood of patients to the ER. Owen must help an eleven-year-old girl after she calls the hospital for help for her mother who is barely breathing. Owen, Amelia, and Richard walk the girl through a procedure to help the mother. The young girl and her mother eventually make their way to the hospital with Amelia being able to save her. Meanwhile, Callie and Maggie treat an elderly, sexually-hyper woman. Maggie confides in Callie about her love life, and Callie suggests she should go out with the radiologist. Jackson and Ben work on a plastic surgery case, which allows Ben to talk about his sister's gender reassignment. Meredith learns from Jo that she is on a successful surgery streak ever since November, which is when Derek left. Meredith calls Derek to share her success, but begins to question Derek when another woman answers the phone.

Absent: Patrick Dempsey as Derek Shepherd

A patient with Alzheimer's is admitted to the hospital after having crashed into a house of a young pregnant couple, with the patient bringing memories to Richard regarding his late wife Adele. It is discovered that the man does not have Alzheimer's, but NPH, which caused his memory loss. Amelia offers to insert a shunt to prevent fluid from building up, but the patient declines, hoping to forget what he has done. The young mother suffers a massive intracranial hemorrhage, and dies on the OR table with the doctors being able to save the baby. Callie's new date leads Arizona to become jealous, but Arizona later reveals to Callie that the woman is a crazy ex-girlfriend. Richard tells Maggie about Ellis' fight with Alzheimer's; however, she reveals to already have been tested for the gene. April and Jackson struggle to move on with their life after the death of their baby. After not answering his phone all day, Derek shows up on Meredith's doorstep.

With Derek back in town, Meredith tries to distract herself from the idea of her husband cheating on her. Alex asks for her opinion on one of his cases with Meredith suggesting a risky surgery. Owen's mother is admitted in the ER, and Owen learns about his mother's much younger boyfriend. This angers Owen, who then lashes out at Amelia. Later, however, Owen comes around and accepts his mother and her boyfriend's relationship. He then apologizes to Amelia, leading to them having sex. Jo's patient, admitted with nosebleeds, turns out to have a leech in her sinus cavities. Meredith's streak comes to an end when her and Alex's patient dies, and Alex comforts her. It is revealed that Derek did kiss his research fellow in Washington, D.C., but Derek proclaims his love for Meredith. Meredith confesses to having learned to live without Derek, but she confesses to not wanting to.

Absent: Jessica Capshaw as Arizona Robbins

A squad of police officers make their way to the hospital to support two of their own: brothers who were shot during the robbery. The suspect was a 15-year-old boy who is also undergoing surgery in need of a liver. It turns out that there's a match with one of the brothers he shot in the robbery. Meredith must discuss the process of organ donation with the mother of the two police officers who were killed, but before she can get the mother's permission, Bailey jumps in asking about the liver for the boy. The mother denies permission for organ donation when she learns who the boy is. Callie is working on the leg of the commanding officer who expresses concern for the young boy. Mistaken as wanting to get even, the officer tells Callie that the boy was a child they were able to get into foster care. With this new information, Meredith is able to convince the mother to save the suspect's life by allowing the liver transplant. Derek comes back to work under Amelia, who thinks he won't be able to work at the hospital without trying to steal surgeries from her. Eventually, Amelia realizes that her brother is being sincere and is happy to be back home with his family and his job as her fellow. With prodding from Jo, Stephanie falls for one of the chaperones on the field trip, but to her surprise, the guy is a high school student. Callie gets asked out by the commanding officer, but indirectly declines without explanation. Amelia confides in Derek that she is falling in love with Owen.

A local chef has his penis cut off by his wife when she finds out that he was having an affair. April calls Catherine Avery for a consult about the chef, and Catherine becomes impressed with Stephanie for her quick thinking about the preservation of the penis, suggesting urology as a specialty. Amelia and Callie disagree on the approach for a surgery for a misaligned spine, leading Owen to weigh in on Amelia's approach. However, in surgery, Amelia's approach goes wrong leading Amelia to blame Owen for interfering. The woman the local chef had an affair with, cuts off the chef's penis again, but Stephanie manages to get the penis back and decides to not specialize in urology. Richard and Catherine proclaim their love for each other after having an argument over their careers. Derek leaves for D.C. to wrap things up, but Meredith gets a call from the White House saying Derek never showed up for the meeting.

A plane crash in Seattle brings old memories back to Meredith, Arizona, and Owen. After learning that Derek never showed up in D.C., Meredith begins to worry; however Bailey gives her a 5:00 p.m. time frame for freaking out. With the plane crash situation, Alex tries to make sure Arizona is okay, but he only begins to annoy her instead. Alex admits to Arizona that it was him instead of Callie who cut off her leg, with Callie admitting to Arizona that she wanted her to have Alex and just be mad at her. Amelia learns about Owen's involvement in the plane crash. Maggie learns from April and Alex about the plane crash that killed Lexie, while Stephanie tries her hardest to make her patient remember the pilot with whom she fell in love. Just when Meredith is about to call Derek at 5.00 p.m., a police car pulls up in her driveway.

Absent: Jesse Williams as Jackson Avery.

On his way to the airport, Derek witnesses a car crash, leading him to try and help. He manages to help a girl with an exposed abdomen and a boy who has suffered a massive head trauma. Derek manages to alert help from the smoke of the car explosion. Just as Derek is about to drive away, he is hit by a semi-truck, and is rushed to the ER at the closest hospital. He is unable to speak as the doctors examine him, with him subconsciously telling the doctors to order a head CT. However, Derek is rushed into surgery, but by the time the doctors discover his blown pupil, the neurosurgeon arrives too late and Derek is declared brain-dead. After several hours, Meredith signs the papers to turn off life-support. She confronts one of the doctors, Penny, and advises her to learn from her mistake. Right before the nurse turns off the life-support, Meredith remembers her life with Derek and tells him she will be fine, and Derek takes his final breath.

Absent: Justin Chambers as Alex Karev, Jessica Capshaw as Arizona Robbins, Jesse Williams as Jackson Avery, Camilla Luddington as Jo Wilson, Jerrika Hinton as Stephanie Edwards, and Kelly McCreary as Maggie Pierce.

Meredith reveals the news of Derek's death at the hospital, with everyone taking it hard except Amelia, who hides behind morbid jokes about her brother being dead. After the funeral, Meredith goes AWOL after leaving a note. Bailey and Ben discuss their different opinions about extraordinary measures if anything happens to them. Dan, Callie's chief of police one-time date, is admitted to the hospital after an accident. Owen and April go overseas for a planned three-month military surgical training program, but April keeps extending her leave despite Jackson's pleas for her to come home. Jackson and Jo work on a pair of burn victims who bond over their circumstances. After almost a year, Alex receives a call from Meredith saying that she and the kids are fine. It is revealed that Meredith is very pregnant with Derek's baby.

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Catherine rejects Richard's proposal before he can even ask her. Callie continues to work with Dan after she had to amputate his leg, and remembers when she and Derek created the robotic limbs. After not letting Derek's death affect her, Amelia has an emotional breakdown at the hospital, leading her to buy drugs. At Meredith and Derek's house, Owen manages to convince Amelia to not take the drugs, which leads Amelia to confront her feelings about Derek's death. On Valentine's Day, Ben reveals to Bailey about wanting to be unplugged like Bailey, but Bailey, now accepting Ben's wish to live at all costs, is disappointed with his decision. April returns from her military leave which happily surprises Jackson, and Catherine comes around and proposes to Richard, who happily accepts. Meredith begins to bleed from her uterus and Zola calls 9-1-1 saving Meredith's life, paralleling when Meredith saved Ellis' life. Meredith gives birth to a baby girl named Ellis, and Alex shows up to support her as he was her emergency contact person. Meredith finally returns to Seattle and decides to start over.

Absent: Patrick Dempsey as Derek Shepherd.

A collapse of a tunnel sends multiple victims to the hospital, and April, Maggie, Amelia, and Meredith are sent to the site to help rescue others. Richard, serving as interim Chief of Surgery since Owen resigned, gives his first-day speech to the new interns on the same day as his and Catherine's wedding day. However, Richard calls off the wedding after several fights between them. Amelia confronts Meredith about her decision to unplug Derek before consulting with her. Callie and Arizona work on Joan, a patient who goes into labor after the tunnel collapse, but one of the new interns loosens her collar, leading the neck to dislocate. Meredith asks Alex if she and the kids can move back in with him and Jo, which leads Alex and Jo to hit a rough spot. Jackson struggles with the new changed April, and Maggie receives bad news from her mom. April brings one of the trapped patients, still in his car, to the hospital.

Absent: Patrick Dempsey as Derek Shepherd

With only five minutes to get April's patient out of the car to the operating table, Stephanie's interns must help make a clear path. Alex asks Jo about Meredith and kids moving in, which Jo misunderstands, leading her to buy a fixer-upper apartment for her and Alex. Meredith tries to mend her relationship with Amelia by giving her Derek's last voicemail. Richard promises Bailey that she will be the next Chief of Surgery, but Catherine disagrees, leading them to argue about their careers. After Meredith tells them to work out their problems, they agree to each have one candidate for Chief of Surgery which the board will ultimately choose. Richard and Catherine get married and have their reception at Meredith and Derek's house. April tells Jackson about wanting to go to Jordan again, but he gives her an ultimatum about their marriage. Maggie consults Meredith about her parents' divorce, and Meredith suggests that they "dance-it-out".