Here are some suggestions...most I've learned here at the DIS.
search engines....
www.mobissimo.com
www.kayak.com
www.onetime.com
I've never actually booked fares from these sites, but use it mostly as a tool to get an idea of the fares...then double check availbility with the airline on the phone.
Hints
Download Southwest Ding program to get great rates
Sign up for email notification of travel deals at airline sites....southwest, airtrans, independence air, and all the airlines you can. Also sign up for the email alerts at travelzoo.com
I have all the airline sites bookmarked, so I can check them from time to time...found a good fare on the American Airlines site, but flying on US Airways by clicking the "More Options" link when choosing dates for the flight...it opens up the option to check "All Carriers".
Check more than one airport. For example, I live 2 1/2 hours from St. Louis, 3 1/2 hours from Nashville, TN, and roughly 4 hours from Louisville, KY, Indianpolis, IN, and Bloomington, IL, and 2 hours from Evansville, IN so I check all those airports when I search fares...sometimes I can get a STL flight cheaper...or most times Nashville is cheaper...just depends on the time and flights.
Well, hope this helps. I've learned alot about checking airfares in the past year from the DIS boards...greatest source of info yet.