How many times have you seriously checked your machines for dust in the vents, your computer desk for dust and dirt, your mass of cables and wires under the desk for Japanese soldiers still fighting WWII? If you're anything like me and have cables running everywhere, no matter how often you think you clean you still will probably find loads of dust down the sides and such.
It's worth unplugging everything once in a while and getting in there with the vacuum cleaner nozzle (the one with the bristles on the end), suck up all that dead skin and the dust mites!
If you have a PC and you're confident with a screwdriver then it's worth taking the cover or side panel off your computer and having a look inside (but not if it will void your warranty on a new-ish machine), if you see dust bunnies then it needs cleaning - they usually congregate around heat sinks and where the processor is; sometimes they can even prevent the CPU fan from starting up so your CPU would soon overheat. Go in gently with the vacuum cleaner, use a long-bristled paint brush (with soft bristles, the kind you might use for painting door frames) to gently pick out any clumps of dust and generally flick it up so that the vacuum can suck it up. The important thing here is not to dislodge any components or jumpers.
It's usually possible to unscrew the main CPU fan to clean under there too, make sure the fins of the heat sink are as clear as they can be from dust bunnies. It is not usually necessary to remove the heat sink, if you do then it could reduce it's effectiveness as it's usually bonded to the CPU with heat sink compound, which would have to be re-applied for it to get the maximum heat transference.
If you don't fancy taking the covers off your machine, just stick your vacuum cleaner nozzle up to the vents and PSU fan around the back and give it a good old sucking, that should remove some dust at least; go all around the machine and suck out any holes or vents you find. Don't do the DVD drive though as that's quite delicate and shouldn't be dusty inside anyway.
You may want to run over desk surfaces with a damp cloth to get the fine dust off before putting all your junk back on there. When all is dry plug everything back in, sit back and enjoy your (temporarily) clean computer!
I take no responsibility for damages mind you, just to cover my own back here.