One of the biggest reasons why was a rash of injuries late in the season that caused that team, which was in first place in early August, to fall apart down the stretch and finish third in the American League East.
With the Red Sox running into similar misfortune this season, it begs the question: can they survive?
In Francona's mind, comparing the two years is like apples and oranges, in large part due to the fact that in 2006 the injuries came fast and furious but were concentrated on the most important position on the field.
"We lost our entire pitching staff," Francona said. "We were getting pitchers from all over the map [to fill in]."
Indeed, while today's club needs temporary replacements at second base and at catcher, it has managed to avoid sweeping injuries to its starting rotation. Josh Beckett has been sidelined for some time and Clay Buchholz may miss a start or two with a hamstring strain, but Francona feels good about the staff going forward.
It was not easy to feel good in 2006, when guys like Kevin Jarvis, Jason Johnson, Kyle Snyder, Kason Gabbard, David Pauley and others were given several starts, some of them resulting in some unsightly results.
With just two pitchers — Beckett and Curt Schilling — making at least 30 starts, the 2006 Sox went 25-38 from July 26 to the end of the season.
Although the rotation has not been devoid of injuries in 2010, it has remained the backbone of a team built around pitching. That gives Francona plenty of confidence that this latest rash of injuries will not cause a collapse similar to that of '06.
"As long as you pitch, you're gonna give yourself a chance and our pitching looks good," the skipper added. "If you're gonna get beat up, you lose pitching, it's gonna be hard to replace."
For the most part, the 2006 season went into the tank when the Sox were swept in five straight games by the Yankees at Fenway Park. While Beckett and Schilling made starts in the series, so too did Johnson, Jon Lester (just 22 and little more than a promising call-up at the time) and David Wells, who was 43 and acquired from San Diego to try to eat up some innings.
The starters combined to go 0-3 with an 8.03 ERA in that series, and Boston never recovered.
Lester, of course, has become the ace of the staff in the four years since, and his complete-game win Sunday in San Francisco — the city which saw the Sox lose Buchholz, Dustin Pedroia and Victor Martinez to injury — simply reinforced Francona's take on the health of the club.
"It's not like we don't love Pedroia and Victor, but if you get a Lester out there for nine innings, it takes the burden away a little bit," Francona said.
So long as Lester keeps going and the other arms avoid the injury bug spreading throughout the clubhouse, a repeat of 2006 will not occur. So says Francona.