CCleaner uses a set of Rules to define what files it can and can't remove. These rules cover everything from Windows Temp files, files that have been put in the Recycle Bin, to old virus definition files that just clutter your hard drive up. CCleaner currently supports over 200 applications.
We spend an enormous amount of time each month checking and double checking these rules to make sure that what we remove is absolutely, definitely not needed.
We also monitor closely all the development of the applications we clean. If they change something, so do we.
You can view the latest rules by running CCleaner with the /export option.
Here is an example rule.
Details of how to understand the rules can be found at http://www.piriform.com/docs/ccleaner/advanced-usage/ccleaner-ini-files/what-do-ccleaners-ini-files-do