I've used a disease in my game exactly once. Some kind of plague carried by space rats. This was d20 Modern, and I'm pretty sure the PCs made all their Fort rolls, so it never came up. It was never intended to be a continuing scenario in itself, anyway. Just a hazard of the encounter.
Mostly this is because up until a year or two ago I only ran d20 games regularly, and d20's disease system isn't particularly inspiring. Add in cure disease, and, well, there didn't seem to be all that much point to the adventure. (I'd love, by the way, to be proven wrong about this. Anyone got some awesome 3e/3.5/d20 system disease stories?)
As an aside, this is one thing that I really like about 4e. The disease track is just a whole lot more compelling. More tension, and more opportunity for interesting effects.
Still. You'd think that at some point I'd have jumped on another way to make my players' characters' lives miserable. Or that some enterprising DM would do the same to me. Hasn't happened yet. I've never even had a game where something like this happened to an NPC. I can understand that there might be logistical issues getting in the way of giving PCs certain diseases (some kinds of games would handle it really well, I think, but a really pulp/action/adventure game might seize up a bit) but there are plenty of things I've avoided doing to PCs for the hassle of it (I tend not to have villains capture just part of the party, for one) that I'll happily inflict on an NPC they like.
Boy, do I ever love abusing NPCs. There's all kinds of things you can do to them that would be a huge headache for the PCs, but are pretty much excellent with them. I try not to abuse them as a plot hook too much, but there's a certain kind of player who will get really attached to NPCs and then get really excited when they get a chance to save them from some hideous fate. And I always like to make my players happy.
Anyway, what makes this really weird is that I tend to love weird afflictions of various kinds in other media. Illness and injury come up with a decent amount of frequency in the fiction I write. In a way, even things like werewolves and the Hulk are just really dramatic examples of "disease," and that kind of dramatic, supernatural affliction is category I really dig. But even that has never really come up in one of my games.
The way I'm putting together the setting I'm working on right now, there's a good chance that this'll come up in a big way in the next game I run, so that should be interesting. But considering the issue has gotten me curious. Any of you folks ever used disease in a game? Was it a one-off thing, or is it part of your regular threat routine? How'd you handle it mechanically? Did it work out well, or are you never touching it again?