Virus scans, i highly reccomend using a free online scanner ontop of whatever regular virus protection you have. I reccomend Trendmicro; http://housecall.trendmicro.com/
Run all your anti-spyware applications too, i usually don't leave that up to one program, usually three does the trick. My favorites are adaware, spydoctor, and counter spy.
Bring up the task manager and look up how many processes are running too. Your computer could be filled with programs that auto-start with or without your permission, which could cause your computer to behave sluggishly.
Also specs of your computer might help, specifically though your processor and how much RAM you have.
Defragging as the guy above me said might help, but in my experince it offers minimal peformance increases. And if you've done it recently (the last 3 months) its completly not worth it, and will probably do your computer more harm then good. Frequently defragging your drive puts tremendous stress on the harddrive, and the results arent anything to justify that stress.