From the Otto on WordPress blog there's a recent post (made more useful by the release of WordPress 3) about how to use the multi-site abilities of this latest version to create multiple sites with their own domain names attached to each.
The other day, Klint Finley wrote a very good walkthrough of using the new Multisite functionality of WordPress 3.0. In the comments, a lot of people wanted to know how to use your own Top-Level-Domains. Since I'm doing that now, here's a quick walkthrough/how-to guide.
He uses the WordPress MU Domain Mapping plugin to get the job done and, via screenshots and a little bit of code, shows you how to use the admin panel to easily set up the domains and the sites they should resolve to.