We do like to joke and have fun. Here, we'll seriously try to scare you. Some of the things we'll warn you about may sound silly; but we can assure you that they do happen regularly, both to the novice and the elite. That's why these are Trade Secrets.
There is no safety net.
You cannot undo bad changes by quitting the Registry Editor without saving your work. That's not possible. Registry changes are "live" - they happen immediately as you type and use the mouse.
Even if you have backups of your Registry, you still must use the computer to restore it. If you damage it badly enough, the computer won't work. The fatal mistake can be made in one click or keystroke.
Don't use Registry cleaners.
Normally, unnecessary data does not hurt the Registry and does not slow down your computer - contrary to the claims of companies who make and sell Registry cleaners. (OK, some are free bait for other products they sell.)
And contrary to testimonials claiming a certain Registry cleaner has speeded up a certain computer, we submit the following.
If the Registry was not damaged, the performance increase was minimal, temporary, or anecdotal - "my computer ran faster" ("now I do this every week").
A Registry cleaner may find thousands of "unused" entries in your Registry. This so called "Registry bloat" is given as the reason your computer is slow; whereas the actual reason is misconfiguration of your system, including damage from Registry cleaners.
Some of these "unused" entries may refer to files and folders which do not exist on the hard drive. You can verify this yourself, so why not clean out those entries? If you intentionally deleted the referenced objects, and if you intend to never restore them, and if your system or applications never use them, then it may be safe to remove those Registry entries.
But this is only a handful of entries - what about the rest?
Understand that your operating system and applications often create Registry entries which are reserved - for record keeping and reference to work spaces where files, programs, and other objects are repeatedly written and deleted during normal operations.
It's a bad idea to delete those Registry entries just because you cannot find the referenced objects at this moment.
Not all damage is immediately obvious - what you don't know can hurt you. If programs and services fail to start, the computer may run faster because it has less to do. Your car goes downhill much faster without the transmission and brakes.
More details - Microsoft MVP forum
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Guidelines for working with your Registry:
A. Our first general guideline for editing the Registry is: Don't.
Most of the useful changes to the system configuration can be accomplished by much safer means, such as through Control Panels and other system tools. However, given that you may need to ignore our first guideline, here's more.
B. Backup frequently with System Restore and/or ERUNT. Use System Restore before every installation and uninstallation (Windows Update automatically creates a Restore Point). Use System Restore or ERUNT before every Registry editing session.
C. Don't work with the Registry until you have at least learned the basics about its structures and functions, and about the Registry editing program.
D. Don't work with the Registry unless you are well rested and alert. If you are sleepy, leave it for another day. The tales of woe are many.
E. Don't leave the Registry editor open while you are away from the computer. Lurking family, friends, coworkers, children, pets, falling objects, and elves await their window of opportunity.
When you next open the editor, it zooms in to the last selected key; plus it has a decent bookmarking feature which you can use to document where you made changes.
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Most changes are made within the major keys "HKEY_LOCAL_MACHINE" and "HKEY_CURRENT_USER". Very few changes are made within the major key "HKEY_CLASSES_ROOT".
Generally, we recommend that you alter nothing within the major keys "HKEY_USERS" and "HKEY_CURRENT CONFIG".
Go to Microsoft.com, search their site for "system registry", and start reading.