AFAIK all serious skinners use Firebug, if you don't stop reading and download it now ;-)
Not everybody knows that there are plugins for Firebug available.
I'm using one for some time now and it is really handy.
It allows you to load an image as an overlay of the website in your browser, which I use a lot to check a skin with the original graphic Design (mostly a PSD file).
The plugin is called "PixelPerfect". (http://www.pixelperfectplugin.com, or the addons page of Firefox)
It allows you to load a JPG of the design position on top of the website set it's opacity and switch it on and off.

A great tool to check how well your skin complies to the original design, a must have for every skinner IMO.
Some Other Firefox extensions that are very handy for Skin developers:
CookieCuller: protect certain cookies and delete the rest
ColorZilla: color picker in your browser
MeasureIt: measure in your browser
HTML validator: The tool to test your site for (X)HTML errors
LoremIpsem Content Generator: Generate Dummy text
Web Developer: A collection of tools for the web developer