Generally, yes, but it's usually not a big problem, unless you're installing and uninstalling programs regularly, or you've been using the same computer for over 5 years
Most of the registry cleaners create more problems than they fix, IMHO.
BEFORE YOU DO ANYTHING, make sure you have complete backups (on two separate types of media) of anything you want to keep, that's stored on that computer.
It'd be cheaper to buy a new computer, than use one of those cleaner programs that hoses your hard drive, and you then have to spend big bucks retrieving your data, reinstalling the OS, and reinstalling the programs you were using.
But others will have a different opinion. Just be careful.