Hi Dennis,
You may want to read the Skinning Overview documentation.
You don't need to restart IIS for any changes with mojoPortal, but sometimes you must reset the application pool the site runs in. To reset the application pool, simply open the web.config file, add a space to a comment, save the file, and then browse to your site again. When skinning, you have to do this to clear the server's cache if you haven't disabled the Cache settings described in the above mentioned document.
HTH,
Joe D.
EDIT: Added the link to the documentation, sorry about that.