System cache cleaning is one of those so-called "maintenance" tasks that you may read about on the forums on Mac OS X guides that has mixed reviews, and typically is not necessary. In fact, when it is done at the wrong time, data corruption can lead to a situation where an erase and reinstall is necessary. I can't reproduce it easily, but I will say I've had it happen to at least three of my clients, so it is not as random as one would hope.
You've probably heard of browser cache, and that's safe to clean anytime you like. One thing you'll notice when you do, is that some websites will load slower, and others will load faster depending on your internet connection, and the frequency those websites get updated.
System cache on the other hand, which you'll find in ByHost and Cache folders in your Hard drive -> Library, System -> Library, Users -> yourname -> Library, are a much more sensitive type of file. These will optimize the speed of frequently done operations on the operating system itself as well as specific applications which require those folders. When one of these files get corrupted, programs won't launch, will unexpectedly quit, will launch and close on their own, and in some cases Disk Utility won't function normally, or System Preference panels won't launch. To avoid these problems:
1. Only do system cache cleaning after your data is completely backed up to your satisfaction, so that a system restore won't waste your time.
2. Do it when no other applications are running, and there are no memory resident programs that may be affected by such cleaning in Apple menu -> System Preferences -> Accounts -> Login or Startup Items. Check the Process or Activity Viewer applications for applications you might have installed.
3. Do not allow the process to be interrupted until it is finished. If any power outage happens, you may be left with a corrupted cache file.
4. Restart the computer when finished.
If you have a corrupted cache problem, attempt to isolate if it is happening just to one account by creating another account with Apple Menu -> System Preferences -> Accounts with admin access and see if it impacts that account as well. Do the following depending on whether or not it does affect that account:
1. If isolated to one user, go back to the user and delete that user's Library folder's cache files relating to system and Launchservices, and log out and log back in the user twice. If it disappears as a problem once, and reappears, something you are running is persistentantly corrupting that user's cache folder, and you may have to move all the non-corrupt files to the new user.
2. If it is not isolated to the user go to the System and Library folders under the hard drive and see if the Launchservices files and System cache files are removed, if the issue disappears on reboot, and if it does, does it reappear after a second reboot. If it reappears after a second reboot, then you have the scary prospect of an erase and install of your system.
3. Restart the computer when finished in either scenario.
Don't use automatic utilities to manage your system or user cache files. If anything only manually clean the cache when it is necessary and you have corrupted files. The cache is there to speed your system, and should otherwise not be touched.
< slight revision thanks to Kappy >