My standard reply to someone running out of space is this advice.
Regaining Hard drive space:
The easiest approach is to assume that the space has been filled up by your own files: documents, but also includes, videos you have downloaded, photos, music, pdf's, downloaded software. As these files have either been created or downloaded by you, you will know where to find them and these are the things to move or delete.
So look in your Movies folder, Documents folder, in the iTunes and iPhoto applications, for excess movies, photos and music that you can move onto an external drive, or burn to a CD, and then delete.
After you delete anything, remember to empty the trash to recover the space on your hard drive.
A couple of times recently I have seen it caused by a failure to send an email with an oversize attachment - it keeps trying, and keeps making copies, which can quickly fill disk space. If it happened suddenly, check your mail folder. Runaway log files can also do it, but usually more slowly - and whatever is causing the excessive log writing will likely have the machine sluggish beforehand.
A good start to recover some space immediately is to shut down and restart. The recovered space won't last, as the system will use it when you start applications, but you can get a bit of breathing space while you poke around for the problem.
You should aim to keep 20GB+ free on your boot disc.