There are four sections in this episode. Greene hides his role in a killer's death, Carter buries a loved one and must deal with his chilly socialite parents, and Weaver returns to work fearing she has been outed. Cleo begins to experience the side effects of her HIV treatment, Benton reaches out to his grieving sister, and the ER deals with patients after a feud erupts at a local talk show with tragedy striking for one person associated with the talk show.

Weaver takes dire action after catching Malucci with his pants down. Greene's teen daughter drops by County with some unexpected news, an abandoned baby in Chen's care seems to have healing powers, and Abby ropes Carter into helping her fix a fishy mistake she made while clearing her stuff out of Kovač's place. Weaver fires Malucci after she finds him in a compromising position and he calls her out before leaving the ER in anger.

Dr. Susan Lewis returns and a simple lunch date with Greene leads to a new job at County General. Abby's attempt to make peace with Kovač is impeded by the arrival of his bartending lady friend. Chen takes drastic action after Weaver strips her of the chief-residency position, and Benton works to save a man who thinks his death will improve his family's financial future while Corday and the team treat a six year old boy who has Edwards syndrome but the parents (David Hewlett and Susan Traylor) may have motives for bringing their ill son into the ER.

NOTE 1: Dr. Susan Lewis returns to the show after five years.

Carter discovers the sad truth about what is ailing his grandmother. Luka is torn over a case where an aging mall security guard may have caused a severe injury to a rude pre-teen. Roger sues Benton for custody of Reese, Nicole gets a grim life lesson during her first day of training as a nurse's aide, and Corday gets a possible lead on why so many of her patients are dying while Greene's daughter Rachel gets suspended from school. A new medical student arrives in the ER and is introduced to his new coworkers.

Romano forces Benton to make a decision about his future at County as the custody trial for Reese reaches its climax. Carter's father drops a holiday bombshell and Kovač's former flame resurfaces with yet another secret. Weaver and Lopez have their first date and the staff pray for a Christmas miracle after a young mom arrives with her critically injured son. Benton departs County after performing a final, near-miraculous surgery.

Training an arrogant intern leads Greene to a life-altering realization about the future of his own medical care and his ability to provide it to others. Elsewhere, a junkie gets a lesson in life's hardships after she goes into premature labor, a museum worker displays signs of a legendary ailment usually attributed to the undead, and Corday is forced to give in to a terminal patient's demands to die with dignity. Greene then refuses treatment and finishes his last shift to spend his last days with his fractured family.

A frantic phone call sends Lewis racing to New York, where she enlists police officers Faith Yokas and Maurice Boscorelli to locate her missing sister and niece. Back at County, Carter confronts Abby about her drinking but fails to sell her on a sober life; Corday gets bad news from Rachel concerning Mark in Hawaii; Pratt annoys Chen and his showboating puts Gallant and a patient in peril.

These are the final days of Dr. Mark Greene's life. He spends them in Hawaii, where he grew up, with his daughter Rachel in the hope that the trip will give the often antagonistic pair a chance to reconnect and heal old wounds before it is too late. The unexpected arrival of Corday and baby Ella, both having been summoned to Hawaii by Rachel due to her concerns about her father's increasingly ailing health allows the weakening Greene to see his fractured family reunited before his death. A few days later, Greene's funeral is held with members of the ER and OR staff all in attendance.