The most obvious change is that regular designated hitter David Ortiz will start at first base, forcing Kevin Millar into a substitute role where he will come off the bench. But there are other significant differences as well.
For example, if Game 3 starter Pedro Martinez is locked in a 1-1 tie in the seventh inning when his turn to hit comes up, Francona will have a tough decision to make.
"There comes a point in time in the game where your pitcher might have to come out even if he's throwing the ball real well -- we're not used to that," said Francona. "Especially with some of our guys, there comes a time in the game in the sixth, seventh, eighth inning when they have two guys up in the bullpen and things really happen quickly. I'm glad that I've gone through it."
Francona managed the Phillies from 1997-2000, and also played seven years in the National League, so he's well versed on the style of play.
The Red Sox are more suited to the National League rules then they would have been if not for the July 31 trades that brought Orlando Cabrera, Dave Roberts and Doug Mientkiewicz to the team.
"I think our team is built well for it," said Red Sox center fielder Johnny Damon. "We have guys coming off the bench, Millar, Mientkiewicz, Roberts, [Gabe] Kapler, Kevin Youkilis, those are pretty good guys to come off the bench, and [Doug] Mirabelli. Those guys are very capable of coming off the bench and giving us a spark."
Status quo for Schilling: While Curt Schilling was walking around the clubhouse pretty gingerly the day after his Game 2 victory, Francona felt the big right-hander would likely be able to go one more time if this series stretches to Game 6.
Curt Schilling / P
Weight: 235 lbs
Bats: R / Throws: R
"We'll do what we always have," said Francona. "Just keep re-evaluating and monitoring and prepare for his next start. That's what we've done the whole time."
As for the breakthrough medical procedure in which the Sox sutured Schilling's dislocated right ankle tendon for his last two starts?
"This isn't something we would do for 30 starts," said Francona. "Just keep preparing for whatever we have to prepare for."
Homecoming for Mueller: Sox third baseman Bill Mueller will be at Busch Stadium for a World Series game for the first time since Game 7 of the 1982 Fall Classic, when he was sitting with his father in the upper deck in right field.
Most of Mueller's family still lives in St. Louis.
"Unselfishly, it's great for my family and friends and relatives everywhere in St. Louis to experience a World Series," said Mueller. "I think it's great for them that the World Series is not only in their hometown, but to know someone and love someone that's playing in it -- I think it's very exciting for them. I'm happy for that."
One member of Mueller's family who will not be on hand is his wife, Amy, who is in the latter stages of her pregnancy.
The baby is due in November.
"I don't think she's going to make it that long," said Mueller.
Staying focused: The Red Sox were no less businesslike on Monday, holding a two-game advantage in this World Series, as they were the day before it started. If anything, the Sox learned from the previous round, when the Yankees blew a 3-0 lead against them.
"We're 2-0 right now and we can't relax," said Sox slugger Manny Ramirez. "We know what happened against the Yankees. They won the first three games, and we came back. We don't want that to happen to us."
Ian Browne is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.