A very effective tool that I use is Spam Interceptor.
Spam Interceptor
What I like about it is that it is completely server based so there is no software resident on your PC taking up resources. I find tools like Norton Antispam resource hogs. It acts as an intermediary between your email pop server and your inbox. You sign up on their website (it is free), and then set your account up so that it points to your email pop server. You then set up your email client to point to Spam Interceptor. So whatever you retrieve into your email client has already been filtered by SI. The spam never even touches your PC.
SI uses a number of different filtering technologies including trusted lists (you can create these manually or import your address book from Outlook, or whatever client you use that has the ability to export to CSV), BlackLists, Spam Ratings, and Authentification. You have control over how much emphasis to place on one vs another. For 10 bucks a year, you can upgrade to a full account and have even more control over other settings like Spam ratings (what rating determines an email to be spam, what is grey, what is not spam) and the mail check interval.
I find that 99% of my spam is being blocked and I have never had any false positives. Even still, you can go to the SI website, log into your account a perodically check your trash folder to make sure that no real email has been deleted.
Another note: Since your email will be on SI's server for a period of time, it requires the same trust you have for your ISP when your email is on their server. Just like your ISP, they receive millions of emails a day and have no interest in reading your mail.
I was flooded with 100+ spams a day, and this tool has eliminated my problem.
Maxwell