Let's say you inherit a Drupal site and the modules folder looks like this:
And being an organized dev, you'd rather it look like this:
So you create a 'contrib', 'custom' and maybe a 'features' folder for good measure and move everything around.
Then your site blows up and starts giving you errors all over the place.
What happened?
You pulled a shell game on your site, moving modules around and not telling it where to look.
If you click the first Google link you find, you might end up thinking you need to disable all your modules before you move them, but who has that kind of time? The easy solution is to install Registry Rebuild, (just clearing your cache probably won't do it).