Episode: Season 2, Episode 27
What happens: Technically, the show's first major death isn't a human one. Izzie adopts Doc when she's bummed out about a patient, but eventually, Meredith and Derek share custody of the dog when George can't handle him in the house anymore. Doc later gets bone cancer, and Meredith (along with Addison and Derek) has to put him down in the season two finale. It's sad because Doc is very adorable and also because, in typical vintage Grey's Anatomy fashion, he symbolizes Meredith and Derek's fractured relationship. (Remember when Meredith likens herself to a train-wreck victim after Derek chooses Addison?!) Not to mention Doc's vet Finn is also Meredith's boyfriend for about a minute.