Is it worth cleaning the registry?

As I understand it, cleaning the registry is not going to really do much for your computer performance if anything. The registry contains thousands of keys and cleaning out a few dead ones won't really make much difference.

This forum post contains some sources that seem to confirm registry cleaning as a mythical performance enhancer.

It will have no effect on system speed. There is an excellent chance it will make your system less reliable.

The registry is a huge database optimized for speed. It doesn't matter if some game left its config options in there. Other programs aren't going to care and Windows can handle the memory usage just fine by paging (i.e. only loading what's needed) and other techniques.

The only time a registry cleaner could be useful is if a program was not uninstalled properly; in this case you might have some specific problem such as a broken file association. But if you are not seeing problems and are just looking for speed you are probably wasting your time. Not only that, but deleting stuff from the registry can break things in subtle or hard-to-fix ways. Hopefully a good registry cleaner backs up all its changes so that you can easily restore your old registry... assuming your computer boots properly after the cleaning.

If your windows system has lots of strange bugs that are due to registry problems you might be better served by re-installing. Before XP I used to re-install Windows every 6 months. Now I almost never have to do it. I would avoid registry cleaners.

I checked the Wikipedia page on registry cleaners.
Looking at Jeff's answer, maybe someone needs to update that with criticisms.

I have used CCleaner often, and in fact, also been suggested registry defragmentation tools.
Mark Russinovich, who I trust a lot with my Windows machines, also has a PageDefrag tool that works on registry hive defragmentation.

A reference to another tool by Mark called RegDelNull that helps to cleanup registry keys with embedded NULL characters.

I also often use RevoUninstaller to cleanup after some uninstalls.
The warning from Mark and others on the risk involved with cleanup should be and is taken seriously.