ER: Mark Greene's very last patient, Orion in the Sky, Season 8, Episode 18.
This episode features Dr.Greene's last day working at the ER and finally coming to terms with the fact he is going to die and he wants to die the way he lived his life. Fans of the show will notice many heartbreaking moments in this episode. Like when he tells the patient that he too knows what it is like to be dying. The 2 most painful moments are when he is leaving for the last time. When he is walking toward the door he makes eye contact for the last time with his longtime crush, Dr.Lewis, and as he walks to the door he responds to Abby's goodnight with a crushing "goodbye". The final scene between Greene and Carter passes the torch from one to the other, but in doing so leaves a huge void the show has never filled. Dr. Greene set the tone.