1) The Windows Registry is very fragile, like a raw egg. Every time you handle it, you risk breaking it. Handle it enough, and it will break.
2) Due to the sheer size and complexity of the Windows registry, manually cleaning up redundant and invalid entries would be practically impossible. Registry cleaners try to automate the process of searching for orphaned entries, missing file references, and broken links inside the registry, and remove them.
3) A popular misconception is that the value of a registry cleaner exists by reducing “registry bloat”. Over 99.99% of registries will not have this problem. It is so rare, that I have hardly ever seen it in my 39 years as a Failure Analysis Engineer. A Microsoft Engineer recommended not to clean your registry.
4) Most registry corruption that we see was either caused or antagonized by a Registry Cleaner. Just say NO!
5) The only time we ever use a registry cleaner is when it is absolutely necessary, from either errors (researched to be a registry issue) or after disinfection of virus / spyware, which can cause registry bootup errors. I recommend only running it if absolutely necessary. avast! Pro A/V combined with Malwarebytes Pro antispyware can help alleviate these issues due to infection.
6) The only Registry Cleaner I use is CCleaner. It is the least invasive, and does the least damage.