The Third Game in the Game Series Formerly Known as Diablo

Yeah, um, adventurers crushed Mephisto's soulstone on the hell forge...not Diablo's.

I think in one of the movies it shows you doing the same thing with Diablo's once you kill him in act 4.

Either way, all of the soulstones were destroyed in Diablo 2.

Some people suspect that the worldstone might have something to do with it. Baal supposedly corrupted the worldstone, which meant that Tyrael had to destroy it (so he claimed.) Some say that Tyrael might have gotten a shard stuck in him or something, and may have gotten corrupted himself. Perhaps Diablo will take over Tyrael's body similar to the hero from Diablo 1. A Tyrael/Diablo combo would be pretty badass.

Some people also theorize that Tyrael might have been bad all along. There are hints of that throughout Diablo 2, and it's not completely unlikely that it could be true. However, that doesn't explain how Diablo comes back.

Diablo is in the trailer for Diablo 3, though, so I would suspect he'll be in the game somehow. Who knows? For now, we can only speculate.