Hey gunzlingr, frank's nailed it spot on.. Comic Book Creator is used by lots of people, I got into using it with seeing some of Toneguns work.
Here is there link:
Comic Book Creator
Assuming you don't have any qualms with Amazon, i think you can pick it up cheaper on there or third party sites.
Others have used different software programs like Frank Mentioned with some very good results, check out Self Modifiers pages for examples on doing your own panels.
With using CBC you can't shift or move the panels on the page, which some people find restrictive, theres pro's and cons to every way and I guess most people just experiment before they come across one they prefer/like.
This was done recently by me, using Comic Book Creator.
Superiorville
If you have any Q's about CBC please ask away and I'll do my best to answer them.