Here are the tips to find the lowest rates on flights.
For international flights:
1. Check on Mobissimo - they search many sites and give you good approximation for the best rate, plus you are able to compare different days.
2. Then check Bing Travel, Vayama and Trabber to see if they have better rates.
3. Once you find the best rate, check with that airline website - most of the time they would have it few dollars cheaper then travel agencies.
For US domestic flights:
1. Check Bing Travel
2. then check Jetblue and Southwest, US Airways - as they do not show up in aggregated searches.
3. Check with airline website and book directly with them whenever possible, as it will be cheaper and easier if anything needs to be changed.