Such is the case in the American League Championship Series, where the Sox will be without third baseman Mike Lowell for the duration of their matchup with Tampa Bay.
Lowell -- nursing a partially torn labrum in his right hip -- visibly battled pain throughout the ALDS against the Angels, receiving a night off during Game 2 in Anaheim and playing through pain in Game 3 back at Fenway Park. He was replaced by Gil Velazquez on the ALDS roster prior to the team's Game 4 win.
That means the infield shuffle method will be used at least through this series with the Rays, leaving Francona to weigh his options prior to each contest on which combination puts his team in the best position to win.
"Things like that have happened all year long," first baseman Sean Casey said. "We've brushed that off and know that we need to keep pushing forward and keep pushing the ball."
Francona's lineup on Monday proved more than sufficient, helping bolster a 3-2 win over the Halos and propelling the Sox into the ALCS.
Moving regular first baseman Kevin Youkilis to third, Boston started August acquisition Mark Kotsay at first. In that scenario with Youkilis moving across the diamond, Casey can also be inserted at first base -- though Kotsay holds stronger fielding and baserunning skills.
Kotsay is primarily an outfielder, having not played first base since 2006 with Oakland before coming to Boston. But Francona continuously applauds his footwork at the position, saying he's more than capable of producing in the infield.
He showed that ability on Monday, tracking down two foul ball pop-ups for outs while also scoring the game's first run.
Lost in the shuffle of first baseman is Youkilis, who is praised by his teammates for making such an easy shift to the hot corner. Youkilis played third most of his life growing up and was molded into a Gold Glove Award-winning first baseman as a member of the Red Sox.
"I think he makes the transition so easily that we kind of take it for granted," Lowell said. "Not only did he go from third to first two years ago, but how he can go back and forth [now].
"You really tip your hat to a guy like that because he allows for so much flexibility."
Francona holds the ability to keep Youkilis at first base on occasion by moving shortstop Jed Lowrie to third base and inserting utility infielder Alex Cora at short.
Cora is generally used when he has good batting numbers against an opposing pitcher. That might be the criteria for being inserted into the lineup, as both Kotsay and Casey provide better offensive production than the 32-year-old veteran.
Still, it's another option for Francona. With Dustin Pedroia at second base being the lone constant around the horn, Francona has a lot of options when making out his lineup card.
Losing Lowell -- the 2007 World Series MVP -- was clearly a devastating blow to the Red Sox's lineup, but one they can overcome just by digging into their resourceful bench.
It's what they've done all season long.
"I think it's been resilient," Casey said. "We haven't made any excuses for anybody. Guys stepped in and played well. We were able to get into the playoffs, and once you get here anything can happen."
Mark Remme is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.