Is getting the best airfare possible? According to this Houston Chronicle article, probably not.
As it turns out, finding the best airfare doesn't just seem complex, it really is an extremely complicated process. Airlines' computer systems are constantly adjusting fares to account for the "millions of possible combinations of fare factors for any given trip." Fare factors include flight times and dates, routes, and airline restrictions.
There are so many factors affecting flight prices that Carl de Marcken, the primary flight-price-calculation whiz cited in the article, estimated that for an American Airlines flight between Boston and San Francisco, "there are nearly 25 million ways to arrive at a fare." See what we're up against? It seems that finding the absolute cheapest fare is a bit like trying to control the weather.
However, I've got to admit I find the news strangely liberating. If there's just no way I can be sure to find the absolute lowest fare, I can adjust my expectations and aim for just getting a lower fare. That way, if my flight cost is in the top ten percent of least expensive flights, I've beaten the odds and can focus the rest of my savings efforts on other aspects of my vacation.