I do the following:
* don't accept mail for non-existing recipient adresses
* don't accept mail where the sender domain is one of my domains, except when whitelisted manually
* don't accept mail from hosts on the NiXSpam list[1] (unlike some others, NixSpam has pretty reasonable policies with automatic delisting after 12 hours)
These three rules together work pretty well, I get only a handful false negatives every day, and virtually no false positives, even though I publish my real mail address on many places in the web, and even used it in usenet, back in the days.
Next step would be using SpamAssassin, but [2].
[1] http://www.heise.de/ix/NiX-Spam-DNSBL-and-blacklist-for-down...