http://www.skyscanner.com
http://www.kayak.com

Also, if you're looking for short-haul flights (ie. in SE Asia or Europe), there are a whole slew of fantastically cheap domestic or intercontinental airlines. Go to http://www.wikitravel.org and search “discount europe airlines” or “discount south east asia airlines”, etc. There is a very comprehensive list. They're usually cheapest either when there's some sort of blow-out sale, or when you book at least 1 month in advance, since the prices rise by number of seats (ie. the first 10 seats are at $20, the next 10 seats are at $50, and so on.)

If you're a light packer, choosing to have a carry-on bag will save tons of money as well – some airlines are now charging about $20 per extra kg which can get pricey.

Flying into nearby suburb airports is often cheaper, too. (ie. Flying into London Gatwick rather than Heathrow) However, be prepared to pay a bit more to commute into the city because the suburb airports might be an extra half hour away.

Red-eye flights are usually cheaper as well, and less likely to be filled up. An important consideration as well is airmiles – if you are currently collecting points with the star alliance group, or have a card with airmiles, etc., try to find flights with partner airlines because you can earn points by flying with them, too. It may not seem like a lot, but the points add up and you can score yourself a short-haul flight after a few purchases, or at least a few nights' stay at a hotel for a weekend getaway.