Yeah I had my niece's computer because it was horribly infested, and there was one I just couldn't get rid of with Spybot or Ad-aware, and before I got my hands dirty I tried WD and it cleaned it right up.
I don't think any single program is really enough, testing of all of them show that there's lots each of them miss, so a combination is sometimes better (or just run a tight system and don't do dumb things is usually good enough).
I've heard good things about this one as well:
http://www.emsisoft.com/en/software/free/
I have a commercial version of Webroot's stuff right now, but when that expires I'm going to try that.