I've eliminated nearly all of my spam, which was approaching 3000 a day. I now route my e-mail through both a pre-server-side filter, Postini, and a client-side filter, Mail.app's built-in system (which is exceptional, and something I've touched on before). Since I've implemented the Postini filters only about two spams per day actually make it to my client, and out of those I've yet to have a single junk e-mail slip through Mail.app's filter — I've effectively seen zero spam for the last two months. I actually thought about adding one more hurdle, maybe SpamAssassin or something similar, but given the complete success of my current method, anything more would probably be superfluous.
The main impetus behind my wanting server-side filtering was that e-mail on my phone(s) had become next to impossible — I needed to catch the spam before it got to my POP server. This is where the deal my hosting provider has with Postini comes in; all of my e-mail is now routed through Postini's filters and then to my POP server after the spam has been stripped away. Postini sees 1.3 billion messages a week pass through its servers and claims that it typically blocks 98% of the spam before it reaches end-users (I'd say that's a fairly decent data set to build effective rules upon).
Another nice thing about using Postini is that I've been able to go back to using Mail.appetizer, something that had become completely useless due to the large volume of spam I was receiving (though this was no longer an issue after the program was finally updated).
While Postini obviously works very well (2 << 3000), I do have some complaints (surprising, I know). The first is simply the lack of end-user customizability with respect to the filters. You're essentially given a sliding scale of what you'll allow to pass through — this scale has just five positions ranging from "lenient" to "aggressive." It's probably just as well that I don't have a million options to play around with as I would spend hours doing just that, but I would like the ability there regardless.
The second thing that really bugs me is the fact that you can't add a group of e-mail addresses to the whitelist (addresses that it will always let through and never hold as false-positives). When you see false-positives and tell it to deliver the message, you're offered the option to add the address to your "approved senders" list, but there is no way to do this in the aggregate — I should be able to upload a file containing all of my contacts and have it add those addresses to the whitelist.