This is a bit of a good one. It could be something and nothing or it could be a real PITA to track down...
I guess if there's talk of Service Packs you're most likely running XP at the moment? Have you made any other config. changes recently at all? Also, I take it Windows Defender has worked at some point and has now died, or is it a new install of Defender that's not worked from day one?
As has been said in the advice above, Windows Defender isn't really the most bullet-proof solution anyway; and one possible cause of it not working is that one 'nasty' or another has got in and broke it on purpose. To that end it might be worth scanning with something like PC Tools Spyware Doctor - that one's not free (officially anyway!), but you can run a trial version that will scan for free (just won't remove anything until it's unlocked) and that might help figure out if it's malware that's broken Defender. Just don't panic too much if it says it's found infections and they turn out to be cookies, so long as you delete those yourself there's not really much harm can come from them (and it's not worth buying Spyware Doctor just for that) - but it may show up something else.
Also, on the subject of putting Vista on... Two concerns here - if your machine is at the 'tired old PC' end of the scale - Vista will probably run a bit sluggishly - and secondly, if you like _all_ your applications to work with the minimum of fuss, wait for the forthcoming Vista Service Pack to go public before you jump in. From what I've found at work until Vista has had a few things fixed it's only really worth having if you need DirectX 10...
Let us know how you get on...
Rob.