Every two or three months, I'll pop out my PC tower, open her up, and get to cleanin'. It usually takes no longer than thirty minutes and keeps the fans running evenly and stress-free, which increases their lifetime and keeps your PC from overheating in the long run.
Here's what I use:
Compressed air
Cotton buds (or "Q-Tips")
Phillips screwdriver (the + shaped one)
Flathead screwdriver (the - shaped one)
Flashlight
Optional: Swiffer 180-degree hand duster. I'd really like to find a 360-degree small duster, but this was the one available at my local Target.