I know it’s a controversial subject… opened for discussion.
http://www.registrytweaker.net/index.php/main/viewArticle/id/8
If you know what your doing, keeping your registry clean and free of junk
is an excellent way to speed up your system.
Unfortunately most users lack the knowledge to do this safely.
Cleaning the registry without proper knowledge or safeguards,
can leave you with an unusable system. (A system that will not boot)
The question therefor is a simple one. Unless you consider yourself an expert,
the few seconds you might save by cleaning and defraging your registry don’t
justify the likelihood of rendering your system useless.
The above is why I recommend using a cleaner such as TweakNow RegCleaner Standard. It lets someone back-up the registry before the first scan, divides the results into 3 categories (safe to remove, not fully safe to remove, unknown), and it is free. I always tell that only the “safe to remove” items are the only ones to delete. I’m sure there are other registry cleaners that work in a similar & safe way for those who are not familiar with the working in the registry.
I still say the registry is best left alone ! ;D
I use Revo Uninstaller to make sure those programs i delete are really gone and don’t leave any registry keys or files/folders behind and combine that with an occasional clean up with windows safety scanner and that’s it. I always make a backup first though.
i think one of ‘top’ ones is CCleaner http://www.ccleaner.com/
It should be fairly safe to use on XP from my previous experiences but i haven’t tried it on Vista yet. I just use it for cleaning out junk files.
Can you tell more? 
Because I’m using CCleaner here too.
It is not as “agressive” in registry cleaning like some other registry cleaners, they(piriform) claim it is designed to be as safe to use as possible. Like i said, i used it in XP and it worked well for me, on Vista i only clean the registry with windows saftey scanner now and then.
The safer and a little bit deeper Registry Cleaner is Wise Registry Cleaner.