Hi,
You should only set those to false while you are designing the skin. Once the skin is completed you should enable caching for best performance.
If you are editing a skin on a site that has visitors, you can't clear the cache in the visitor browser, so the best thing to do is whne you complete all changes make a new skin folder with a version like myskin_v2, copy the skin files to the new folder and then set the site to use the new skin name. This way all visitors will get the new design since they have not cached the new skin yet but may have cached an old version of the older skin.
Hope it helps,
Joe