I most cases registry cleaners aren't required and may do more harm than help. Performance increases from them are tiny, and the risks are huge

The exception is possibly when you're having problems uninstalling a particular program that won't uninstall properly but even then you are taking a shot in the dark.

They also pose a significant security risk, as you're effectively giving some unknown bit of software free reign to do whatever it likes to your computer. Some of these 'cleaners' allow the installation of spyware onto your system. Others (in the case of my fathers computer) actually are major pieces of spyware. In this case then its time to rebuild your system from scratch.
Source(s):
http://www.edbott.com/weblog/?p=643

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