One of the best plugins for Wordpress is Akismet, the centralized spam filter. It picks up almost every spam comment on this blog and has had very few false positives. It also learns from comments that you mark as spam so it’s likely to just get better. It’s probably the sole reason I’ve been able to keep comments open and not 100% moderated. I don’t get much traffic so it’s not as huge a difference for me but it has blocked 600+ spams since I recently upgraded it and has helped with some recent spam floods I’ve gotten.
Well now MT users can also benefit from the Akismet API with their own plugin. Looks like it’s still in development but if you suffer from spam then give it a whirl.