Season 6, episode 24: "Death and All His Friends"
Even for Grey’s Anatomy's standards, this intense episode is bound to send even the toughest viewer into a puddle of panicky tears. It extracts the strongest performances from Ellen Pompeo and Sandra Oh, whose characters witness their significant others on the brink of death. Gary Clark, a man grieving his wife's death, comes into the hospital with a gun. After killing a few of the doctors, he shoots Derek in the chest. Though only a resident, Cristina decides to perform surgery on Derek. Everything is fine (which, in Shondaland, is code for "nothing will be fine") until Gary comes up and points a gun to her head. Meredith asks to be shot because she's Lexie's sister, Derek's wife, and Richard's closest thing to a daughter. The one good thing that comes out of this heart-shattering episode was the (temporary) reunion of Callie and Arizona, who decide that life is just too short to stay mad at each other. Side note: Before tearing out our hearts on NBC's This Is Us, Mandy Moore also guest-starred as Dr. Bailey's patient in this episode.