I've used RegSeeker for over two years now. I know of its use on 6 different machines, all with no problems.
The reason I recommend this program to friends is because it is NOT as aggressive as some of the other registry cleaners. As such, I have never known it to hose a system or break any application or associations.
I am in the middle of testing 12 different registry cleaners (for XP, though I think most work with 98 et al).
I must say at this point that RegSeeker gets big points for being free. And it will find over 1000 things to clean on many systems that have never been scanned. A caveat: It will also find some that keep reappearing on every reboot (on my machine, anyway.) These are associations that different programs keep reapplying. and are not necessarily to be viewed as problems.
But if you're searching for something that is capable of cleaning even more, the best I've found so far are Regsupreme Pro and Perfect Companion.
If you want to talk dangerous, get Registry Drill. That one IS for high end users.
You can also get your cleaners going in circles. You may clean "Registry Entry Test", only to later see "Registry Entry Test.1". This means you've probably gone as far as you can for this entry. You will also find that different cleaners pick up different things. You can keep going in circles until they've all been reduced to their minimums.
So, don't be afraid to dig in, just backup your registry. My backup.reg is 26 MB and compresses to 1.6 MB.
Also, when you've finished cleaning up, make sure to use the free RegCompact utility.
Hope this helps.
Huggy