I use ZoneAlarm, AdAware, Spybot, MS Antispyware, Spyware Blaster, and Norton AV. Plus I have turned off Messenger, locked my raw sockets, and turned off DCOM.
I just cleaned up one of my daughter's computers, and she had 65 pieces of spyware on it.
It's too bad, because having all those security programs resident in memory slows things down somewhat. Zone Alarm and Norton take a couple of minutes to load after bootup, as well. But you are slowed down a lot worse when spyware loads itself all over the place.
The home PC had 267 malware infections last summer ( before I put it and the backup PC behind a hardware firewall ) but my wife's "lobby computer"-- the one guests at her place of business use- had an astounding 1,167 bugs ( not just viruses, trojans, dialers, and tracking cookies, but changes to the registry as well ) ... we did eventually get it cleaned up. What a mess.