Where to start...
Anyways, usually when I leave my main machine on for more than 24 hours (I've left it on for a week before without reboots). I get a wierd windows mood. All windows don't respond, I can't open anything, wierd error messages. Funny part, Ctrl-Alt-DEL shows explorer using 50 megabytes of memory. (even task manager loses windows) Funny thing, after I kill explorer, and execute it. Everything is fixed for another day.
Anyone know a long-term fix?

That could be almost anything... could be your firewall blocking a program you installed... For example, I recently built a computer. Then it would mess up when the screen saver would activate... found out the wireless modem I had needed an update. Did that, everything was fine. I figured out it was that because when it would come on the wireless connection icon would be red instead of green. Shi**y software by others is a large portion of windows problems.

Could be malware or another nasty eating your RAM. Or perhaps your just leaving it on too long :P. How much RAM do you have?

1028 Megs. I run virus checks, adware/spyware/malware checks all the time.

Tbh, this is probably just Microsoft for you. Why do you need to keep your machine on for that long period of time, and if its for server applications then why not switch to a more stable and better designed OS like, oh, i dunno...Linux?

Is it too much of a effort to restart at least once a week? It is probably Microsoft as daniel says.

Thanks :)