9 Ways The Simpsons Could End

Jumping from the "how" to "why" for just a moment, this would seen to be the most obvious reason for the show to end: a voice actor leaves the show for whatever reason and as a result the whole thing wraps up instantaneously. Between just six of them - Dan Castellaneta, Julie Kavner, Nancy Cartwright, Yeardley Smith, Hank Azaria and Harry Shearer - the main cast cover pretty much every major and supporting character in the show, and for any one of them to depart would require a massive reshuffle; the handlings of the deaths of Phil Hartman and Marcia Wallace were respectful, but their characters weren't as integral.

However, this eventuality may not actually spell the end of the show. The manner with which Harry Shearer's near-departure a couple of years ago was dealt with - "We don't need him or his trophy," essentially - suggests that instead we'll see attempts to keep them around (if possible) and it coped with otherwise. Whether that's done by writing out characters or recasting is up to the showrunners, but it doesn't seem all that likely a voice actor leaving would be the end of the show directly.

However, it would certainly put it on life-support, risking angering fans and bringing about one of the other possibilities.