What's the difference between an "online travel agency" (OTA) such as Expedia, Orbitz and Travelocity vs. so-called "meta search" travel site such as TripAdvisor Flights? For one thing, online travel agencies have toll-free numbers with agents standing by to help you book or re-book a flight; meta search sites such as Kayak don't, because they don't sell airfares; they send you directly to airlines or to online travel agencies to book. Both an online travel agency and a meta search site will let you know if the best deal is on a combination of airlines (say, going out on US Airways and coming back on United).
But neither type of site will show you fares on all airlines (Southwest and Allegiant are excluded) and neither will always have fares that the airlines are keeping for their own websites (airlines sometimes hold back fares and inventory for their own sites in order to entice users to book direct).
But, unlike airline sites which try to keep you on the airline's own network, OTAs and meta search websites do show you the widest range of schedules and fares. Occasionally, an online travel agency such as Expedia or Travelocity will have fares that meta search sites don't. For example, over the summer American Airlines had business class fares to Europe for peak summer travel at prices lower than economy class for the same dates; Travelocity had these deals, Kayak didn't. In general, however, meta search sites do a better job of finding "airline-site-only" fares than do online travel agencies. On the other hand, online agencies offer air plus hotel packages that can sometimes save you serious cash, whereas meta search sites don't.
Bottom line: you need to consult meta search sites, online travel agencies, and airline sites if you really want to find the best deal.
Follow Airfarewatchdog on Twitter @airfarewatchdog to track unadvertised airfare sales that sometimes last only a few hours.