Point of fact, just before Thanksgiving when we were prepping the dining room for the Christmas Tree (which didn't get put up til the very week before Christmas, mind you) I bumped the tower and a pad of the most disgusting nicotine-flavored cat hair and dust clump fell off the front vent.
With just iTunes running paused, the fan ramped up to full speed.
So I cleaned it.
Unplugged it, wiped off the outside of the case with a dry woobie t-shirt, and hauled it outside with my little tank vacuum. Carefully blew out the case on low and used a chopstick to stop the fans from spinning while I hit them and their heatsinks with high. Strangely, the only heatsink to gather much dust was the northbridge; the processor sink and graphics sink were relatively clear.
Then I used the vacuum with a small brush to clean off the vents.
It's a Dell E510... the inset vent/grill was tremendously disgusting (I haven't stopped sneezing and it's been over a half hour) and it took two washings with pumice-based soap to get the brown off my fingers :(
Now when you boot it up you hear the hard drive, not the fan - as it should be - and even under heavy load (WoW + iTunes + FF) it is barely audible.
Remember folks, heat is a major antithesis to computer functionality. Dust clogs the system, blocks vents, fans, clutters cooling surfaces... leading to heat.
Heat causes degraded performance, and in the long run can cause component failure.
Take care of your hardware, just as you take care of your software.