We use 2 layers of defense: RBL(bl.spamcop.net and sbl.spamhaus.org) and also McAfee GroupShield.
Concerning RBLs, it was recommended at Lotusphere that for large or busy mail servers you keep the number of blacklist servers to 2.
What I like about GroupShield (aside from stopping viruses) is that it allows me to use basic word lists to stop VERY offensive words.
Also, if you're concerned with false positives from the RBLs; we found that spam is definitely more of a problem for some users than others. So we simply flag blacklisted messages, and then use an agent in the mail file to process the flagged messages according to the users preference. This allows heavily spammed users to delete the junk because they are more tolerant of false-positives; but other users can just move it to a folder.
For more info, see my blog (March 28 & 29)
http://chris.brotherhoodmutual.com/dev/adminotes.nsf/BlogByMonth?OpenView&RestrictToCategory=03-2003
Or Kai Wilzer's DominoPower article
http://www.dominopower.com/issues/issue200305/00001039001.html
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. . . . . . RE: Spam List (~Isaac Optoober... 23.May.03) 
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