Kovač and Sam report Alex missing to the police and suspect that he is trying to find his father. They are especially worried because Alex is diabetic and he has forgotten his insulin. Meanwhile, Lewis and Pratt guide the new R2s on managing their new interns while the irresponsible Morris takes a nap; Ray and Neela back up the board due to poor communication, while Abby shines at managing but fails to properly teach.

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NOTE: Final regular appearance of Dr. Susan Lewis.

Ray attends to a surrogate mother who goes into labor prematurely after being involved in a car accident. A difficult decision must be made as the baby's life hangs in the balance. Pratt gets a visit from his estranged father Charlie (Danny Glover). A depressed Kovač copes with another failed relationship when Sam announces she's moving out, but he gets emotional support from Abby, who joins forces with Neela to put a spoiled, rude patient in her place.

It is a bad day for Kovač as he and Sam can not be civil after their disruptive break up, and a new nurse manager, Eve Peyton, enforces her strict and efficient new procedures. Abby treats a rollerblading single patient with an increased risk for breast cancer due to mutations in her BRCA1 gene, who is struggling with the need for a mastectomy, and Abby makes a discovery about Dubenko's own health while visiting oncology. Dr. Weaver mentions that Dr. Lewis is interviewing for a tenured position and won't be in. Neela prepares a care package for Gallant. After Luka and Sam reach a tentative peace, he gets drunk at a bar and Abby gives him a ride home.

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NOTE: First appearance of Dr. Eve Peyton.

In the wake of heavy rains, the ER is flooded with diverse patients, including a baby involved in a suspicious car crash with her mother and a heart-attack patient visited by his sex therapist. Sam confronts Eve about her strict ways. Abby learns the details of Dubenko's condition and tactfully refuses his advances. Kovač protests when nursing home workers drop off Blaire Collins (Stana Katic), who has been comatose for six years, for routine care, but later in the day, she unexpectedly regains consciousness.

Kovač bonds with Blaire, who has no memory of the carjacking and rape-murder incident that caused her coma, while her drug therapy becomes an issue. In the wake of Lewis' sudden departure, new attending physician Victor Clemente arrives to help make the ER more efficient, but the residents are not too fond of him, despite his wide-ranging knowledge. Abby's breast cancer patient convinces her to take a long-delayed exam. Ray begins a sexual relationship with a young woman named Zoe Butler (Kat Dennings).

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NOTE: First appearance of Dr. Victor Clemente.

Clemente, Abby, and Neela secretly care for an infant chimpanzee. Eve promotes Sam and assigns her a dreadful task: she must fire a beloved and long-time nurse, Haleh. Pratt reaches a decision about his relationship with his estranged father and learns the truth about his father's abandonment of him. Ray discovers Zoe has chlamydia and that she's underage.

The treatment options for a 10-year-old victim of a shooting- who has already been abducted and sexually abused for months- sparks a furious argument between Kovač and Clemente, which Abby becomes stuck in the middle of. Paramedic Tony Gates flirts with Neela, who is awaiting Gallant's arrival, which is unexpectedly delayed. When the little girl dies, Abby takes out her grief and frustration on Kovač and they kiss. Ray is confronted and beaten by Zoe's father.

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NOTE: First appearance of paramedic and medical student Tony Gates.

Kovač and Abby wake up together, but decide to remain friends. The ER prepares to take in victims of a plane crash into an apartment building, while Neela (still doing her mandatory paramedic stint) and Pratt head out to the crash site because Pratt doesn't trust Ray in the field. Neela distinguishes herself with a field surgery and a rescue, impressing Dubenko. Sam re-hires Haleh when the ER runs short on nurses due to a training session. Neela gets a surprising visit.

Back from Iraq, Gallant surprises Neela by impulsively asking her to marry him. Morris stands up to Weaver on a patient's course of treatment, and Weaver decides she needs to fix up her own life. An HIV+ mother, who does not believe in the virus, is putting her infected son at risk and enraging Clemente, but it is Sam who is able to help the situation. Kovač and Clemente continue their ongoing rivalry as they vie for the same job, which Kovač eventually gets. Neela and Gallant marry, and Kovač and Abby realize they want more than just friendship.

Kovač arrives for his first day as Chief of Emergency Medicine wearing a Santa hat, with presents for everyone. Pratt and Weaver try to make a Christmas miracle happen for a young girl whose life hangs in the balance after two gang members randomly shoot her. Haleh holds her annual choir tryouts, Eve crosses the line with a disruptive patient and pays for it, Clemente gets a visit from Jodie, a past lover. Abby has a surprise for Kovač: she's pregnant.

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NOTE: Final appearance by Kristen Johnston as Dr. Eve Peyton.

Abby and Kovač agonize over what to do about her unexpected pregnancy, with Abby eventually deciding to keep the baby despite her fears that it might be bipolar like her mother and brother. Neela and Kovač help a religious teenager weigh all her pregnancy options, but differ on what course she should take. Clemente's past is starting to catch up with him as police visit to investigate a missing person report on Jodie. Weaver falls on the ice and realizes she needs surgery.

With Abby now expecting, she and Kovač venture out for some baby shopping. Ray helps Zoe escape from her abusive father, and Dubenko volunteers to take on the dayshift but is overwhelmed. Pratt falsifies a blood test to help a friend avoid a drunk-driving arrest, and Neela gets unexpected and unwelcome news from Gallant.

Dr. Nate Lennox (James Woods), a former professor and mentor of Abby's, is brought into the ER in the last stages of ALS disease. In a series of flashbacks at County, the progression of his illness over the last six years is shown. He wants to give up, but Abby is determined to give him the strength to keep fighting.

An unexpected visitor – Jodie's violent policeman husband Bobby, from whom she has filed for divorce – puts Clemente in the middle of a domestic dispute that ends in Bobby shooting Jodie and Clemente. Kovač and Abby await important test results regarding their baby. Neela struggles with her surgical elective, and Ray tries to convince a homeless musician to accept help from his family. Jodie survives life-threatening surgery but is comatose, and her out-of-context remarks lead to Clemente being suspected in her shooting.

Carter works in the Sudanese desert, helping treat hundreds of diseased people including a woman raped by a militant group. Back in the ER, the police accuse Clemente of shooting Jodie. Pratt and Neela work to save a 14-year-old involved in a hit-and-run accident, but Pratt is infuriated when he discovers who hit the young teen. Kovač refuses to let Clemente return to work until he is reviewed by the Impaired Physician Committee. Jodie awakens from her coma and tells the police about her shooting, and Bobby threatens Clemente's life.

Weaver must make a difficult choice about having hip replacement surgery when the pain interferes with her work, ultimately deciding to go forward with it, and asks Abby to take care of Henry if something goes wrong. When Abby discovers that one of her patients has contracted meningococcemia, the E.R. is briefly quarantined. Sam treats a man who collapsed, Richard Elliott (Armand Assante), who offers her an intriguing job she might not be able to refuse. Meanwhile, Neela decides to attend a support group for military spouses but when she offers her skeptical view of the war, the meeting turns into a debate. Pratt confesses to Kovač that he falsified a blood test; an infuriated Kovač suspends him for five days while deciding his fate.

Kovač, with Abby's help, works feverishly to save a young Turkish woman with multiple stab wounds. Kovač and the woman's mother connect as she shares her experiences from her former life in Turkey. As the girl's condition worsens, Clemente steps in and decides to try a risky procedure; surprisingly, he and Kovač work together effectively for the first time. Sam accepts a part-time job working for Richard Elliott. Neela pulls an all-nighter in preparation for a speech at a surgeon's convention but is disappointed when her speech goes awry. Morris' past catches up with him.

A case involving two teens injured in a car accident proves baffling as the doctors try to determine why the girl is unconscious and why her male companion is so hostile toward the police, before Ray discovers the problem: he's deaf, and the cops (not understanding his sign language) jumped him. Neela copes with a visit from Gallant's bickering parents and Morris gets a tempting job offer from a pharmaceutical company. Olivia learns of Pratt's philandering. Kovač tells Abby that he is going to Darfur to help Carter, but when he realizes Abby is worried, he tells Pratt to go and responds to Pratt's protests by saying it's not a request but a do this work-or-you're fired order. Sam enjoys the perks of working for Elliott. Ray struggles with some unresolved feelings for Neela as she decides to move back to Abby's apartment.

Jodie's husband's harassment is getting to Clemente, making him twitchy. Morris has taken a job with a major pharmaceutical company. Sam's ex-boyfriend Steve arrives at the ER complaining of a stomach pain. Clemente wants to release him but Neela thinks he needs to remain in the ER and is proven correct when Steve displays appendicitis. Morris and Dr. Albright argue about a patient, and after Morris is proven correct, they make out. After hip replacement surgery, Weaver no longer needs a cane to walk. Pratt arrives in Darfur; after he is greeted by Carter, he quickly notices the scope of the horror there.

Pratt's work in Darfur brings him into contact with an injured Sheik and his pregnant wife. The Sudanese police hound the couple because of their political importance and prevent Pratt and Carter from caring for the Sheik. His wife delivers the baby while he is imprisoned and develops post partum complication that necessitate transporting her to a surgical center. On the way Pratt and Dakarai (Eamonn Walker) are attacked by Janjaweed soldiers and Pratt must continue the journey alone.

Gallant is killed in a roadside bombing in Iraq. Clemente's behavior spirals out of control along with his paranoia about Bobby, and Kovač is forced to take serious action when Clemente smashes a passing taxi outside the hospital and is diagnosed with PTSD. Dubenko offers Neela a surgical residency, but she and the rest of the staff then learn about Gallant's fate. Pratt readjusts to American medicine while treating a seriously injured family of two sons and their father and learning the cause of their injuries. Neela watches Gallant's "farewell" tape.

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NOTE: Final appearances of Dr. Michael Gallant and Dr. Victor Clemente.

Luka spontaneously proposes to Abby and is disappointed in her response. Anspaugh and Weaver discuss liabilities arising from Clemente's erratic behaviour, including whether Kovač is doing an adequate job as Chief in the ER. Pratt convinces Neela to attend Gallant's graveside funeral. Archie tries to film a memory video in the ER as he prepares to depart for his new job. Among patients brought in are Steve and another inmate who had a fight. An EMT shadowing Sam for the day turns out to be the other inmate's girlfriend and overpowers a police officer to free them.

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NOTE: This is the last episode until the series finale in which the opening theme by James Newton Howard was used.