I've bought quite a few Steam-redeemable bundles lately, so I've been installing a heap of games on Steam. I suddenly noticed that on my Steam library "The Binding of Isaac" was marked as uninstalled, which I knew for a fact to be wrong.
After taking care to preserve my save files, I went ahead and told Steam to install the game, which apparently jogged its memory (but only after "preparing" the game's files for installation).
So while there appears to be no harm done, I've never had this happen before, and so I wonder if this is some sort of ominous sign.