Ok, first for 50 people you may be in a good place to take up managed filtering. Check out Postini, MessageLabs and Email Systems to name a few. These are professional top quality managed filtering services. This is $2-4 per user per month and includes anti-virus, anti-phishing and such. This is also extremely easy to set up and remember, somebody else is running it for you. This is utter bliss really.

I am personally using my own mail server and I did the simplest possible thing - every incoming connection is checked against dnsbls: sorbs, spamhaus and spamcop (all three allow you to look up addresses for free). This blocks nearly all spam and after nearly a year I've never had a false positive.

If you are into setting up and running something yourself, you can use spamassasin (free oss). This is not terribly hard to set up, but worried about false positives I never really used it. I am filtering for a small number of savvy people using Thunderbird...

Speaking of which, thunderbird has a reasonably decent filtering feature. It takes a while to 'learn' but it has been quite useful in filtering out the few leaking spam messages from dnsbls.

There are countless commercial packages and I bet somebody else will cover that. Hope this helps