Start with Kayak

Ironically, the best site for booking a flight is not one that actually books flights, like Expedia, Orbitz or Travelocity. What you want instead is a meta search site that scans the fares of multiple airlines and travel booking sites simultaneously and sends you to the source to book the fare you want.

Kayak.com is the best option, but even this mega meta searcher doesnt pull up departure info and prices for every airline. To fill in the gaps, check Mobissimo.com and DoHop.com, which are good for locating flights overseas (within Europe especially), and Momondo.com, which says it scours more than 650 websites for the cheapest fares possible.