I'm assuming you run XP:
1. Try to defrag in safe mode. That sometimes work. It takes longer but the result is much better.
2. Run CCleaner first. That will also help a bit.
3. Do you have old programs that you don't use anymore? Uninstalling those will also contribute to a solution.
4. There is an application called Secunia PSI. Installing that and running it in Advanced mode can sometimes reveal leftovers form old Java, Flash etc. Getting rid of those will give you a bit more space. Link:
http://secunia.com/vulnerability_scanning/personal/5. If you're sure you don't have any malware deleting old restore points can help a lot
6. Delete the icon cache file, IconCache.db. It rebuilds by itself but will be smaller in size. Path: Documents and Settings/Username/Local Settings/Application Data
7. Visiting the scanner in my signature will also help.