I worked for a reputable international airlines for years - so I thought I put in my two cents.

The key in finding the cheapest fare for a domestic destination (this includes Canada, most of the time) - is how far ahead you purchased your ticket. This would definitely need a good, firm plan. For example, if you know for sure you're going from San Francisco to Chicago this summer, feel free to purchase your ticket now. Opt for the most restricted ticket, which will give you the cheapest fare - yet, also be prepared for 'no changes allowed' restrictions, i.e. no changes to your travel plan or you'll loose your money. Going to the airline's website will give you the best price, most of the time.

Whereas for overseas travels, when and what airline will determine how much your fare is going to cost you. If you don't have to be in a certain place at a certain period of time, then by all means, avoid high/peak season (i.e. holidays, summer/winter holiday). Travel during off peak season would save you hundreds of $. Choosing which airlines to fly with is also another key. You get what you pay - that's for sure. If you don't really care about inflight service, what kind of food they serve on the flight, then save some $ by flying a '2nd class' international airlines. Make sure you call different travel agents and ask for their quotes, as well as go to the airline's website and look for their off-peak season deals.