It was announced a couple days ago that Harry Shearer has decided to leave the Simpsons after over 25 years as a member of the main cast. I think that Shearer would be the first major cast member to leave the show. Previous departures (including the tragic loss of Phil Hartman) meant that only some minor characters would need to be written off or recast. While Shearer doesn’t voice any of the main characters, he does do voices for many of the most important minor characters. He’s the voice of Ned Flanders, Mr. Burns, and Principal Skinner as well as many others. Shearer is fairly old and has said that he would like to do something new for once, which is understandable given how long he’s been on the show.
The producers say that they will recast most of Shearer’s characters. Obviously, it would be too difficult to just not show his characters again, as many are too important to just let disappear. Nevertheless, it’s hard to see this as anything but the beginning of the end for the Simpsons. The whole main cast has been around for decades, and the show is too iconic to remove any main characters or recast their voices. In fact, that is the sort of thing that the Simpsons would have lampooned while the show still had the vitality that it lost years ago.