I'm using Microsoft's AntiSpyware Beta because PCWORLD told me it was the best protection. As for a firewall and antivirus, I'm using ZoneAlarm Security Suite 5.5 with CA's antivirus built-in.

What, in your experiences has been the best?

There really is no "best", as they all use different methods of searching out spyware/malware.
That's why it's suggested that you use more than one program for the detection/removal of Spyware.
What one misses, hopefully the others will catch.

The programs I use are:
a² free - a complementary product to antivirus software which is specialized in protection against harmful software. Antivirus software often features an inadequate protection against Trojans, Dialers and Spyware. a² fills this gap.
Ad-Aware - A good program similar to SpyBot S & D.
Spybot S&D - Detects and removes spyware, of different types, from your computer.
SpywareBlaster - A good program that prevents spyware from being installed on your computer in the first place. This program is always running in the background, protecting your computer. It prevents the installation of bad active X controls found in web pages.
SpywareGuard - A nice compliment to SpywareBlaster. This allows you the option to prevent downloads that contain bad active X controls.