When news broke last night that Harry Shearer — responsible for literally several dozen voices on The Simpsons — would not be returning to the show, the fate of Springfield characters he spoke through wasn't clear. Speaking to Esquire and The New York Times, showrunner Al Jean confirmed that Ned Flanders, Mr. Burns, and other major Shearer characters will be recast. "We do not plan to kill off characters like Burns and Flanders but will recast with the finest voice over talent available."
In its 26-year history, very few characters have died (Treehouse of Horror episodes notwithstanding), but it's not without precedent — most notably Maude Flanders in 2000. Characters have, however, been retired; both Lionel Hutz and Troy McClure faded into the background after actor Phil Hartman died.
So yes, while some of Shearer's characters will undoubtedly not speak up in Springfield anymore, the major ones — we're guessing Otto, Reverend Lovejoy, Waylon Smithers, Dr. Hibbert, and Principal Skinner in addition to Burns and Flanders — will continue with just a slight change in tenor.
The show must go on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And on. And so forth.