To tell you the truth, I've never used an anti-virus program. I use Windows firewall which amounts to very little, AdAware once in a while, FireFox, and I am careful and aware of potential threats. I can't stress the importance of using FF. IE has gotten better with the latest release, but it still lacks the stability when it comes to vulnerabilities (mallware, adaware, spyware, etc).
I also keep my hard drive image on a server and on an external hard drive, which means if I do get something sticky icky, I can just reformat and reinstall. I've done it enough times that I can actually go through the whole process in about 2 hours.