I assume you mean reinstall the OS when you say "reboot the entire machine."
Assuming so, it's not actually that difficult.
1) Back everything up. You can use Time Machine if you're on 10.5, or just download the free Carbon Copy Cloner and clone your internal drive to your external.
2) Dig out either the discs that came with the Mac or, if you've upgraded the OS since then, your OS install discs. If you're on an Intel Mac and aren't yet running 10.6, this might be a good opportunity to buy a copy for $20 and upgrade while you're at it.
3) Insert the install disc and reboot the machine, holding down the C key.
4) Do an "Archive and Install" with the option "Preserve Users and Network Settings" selected:
http://support.apple.com/kb/ht1545
5) Let it run. You should end up with a full, clean copy of the OS, but all your applications and user settings will still be in place.
4b) You can, alternately, completely erase the hard drive and install a fresh copy of the OS. Then, when it asks if you want to migrate from another Mac, say yes and point it at your external drive. It should be able to bring over all the necessary settings from that drive and get you back to where you started.
If you want to be really thorough, you could do 4b but not import any applications, just users. You'll need to reinstall any software you had, but then there won't be anything left over to cause problems.