The game at Comerica Park is just the first chapter of 162 on the docket for what should be one of the most fascinating Red Sox teams in recent memory.
"We'll be facing Justin Verlander, and it's probably going to be about 40 degrees," said general manager Ben Cherington. "I don't know if that's something you really look forward to. But it's exciting because I think more than anything, I know the group of guys in the clubhouse are really ready to go be the Boston Red Sox again."
Unlike a year ago, when expectations had skyrocketed around Boston following the additions of Adrian Gonzalez and Carl Crawford, there has been less buzz around the Red Sox this year.
But the prognosticators are about to give way to the players -- and not soon enough for the Red Sox.
"You can't put anything into it," manager Bobby Valentine said of those in the prediction business. "If I don't know what my team is going to look like, and what the competition is going to look like, how the heck could anybody else? That's the way I look at it. Who knew what Arizona was going to be last year? No one. Zero."
Valentine -- after several years managing in Japan, then the last couple as a broadcaster -- has worked tirelessly in his return to the Majors.
His eyes have been in constant motion, and he likes what they tell him.
"We expect to make the playoffs," Valentine said. "Motivation is all self-motivation. That stuff doesn't come from the manager, it doesn't come from the press, it doesn't come from the fans. The individuals are motivated by needs and desires."
Within the clubhouse, there are several proud veterans who are sickened by what took place last September. Now, they get to start fresh again.
"I'm excited. I'm excited to go play," said second baseman Dustin Pedroia. "Last year, the end was tough, but we've got to regroup together and come out and play good baseball and do it all year long."
All year long is the key. Last year's Red Sox had multiple personalities. They started 0-6. Then, they played glittering baseball (82-51) for four months. And it all crumbled with a finish (7-20) that was hard to fathom.
"It's a new season," said Red Sox slugger David Ortiz. "I think a good way to start things is being positive. It looks like everybody is ready to go. This year is going to be a challenge, like some other times. It's a year everybody has to come in and pull themselves together and try to change things around."
Sure, there are questions.
Will the untested back of the rotation hold up? Can enough people step up in the bullpen?
"I don't think anybody is taking us lightly," said right-hander Josh Beckett. "We're still a really good team."
Offensively, Boston has the MVP runner-up in Jacoby Ellsbury. They also have Pedroia, Adrian Gonzalez, Ortiz, Youkilis and, eventually, Carl Crawford, who will start the season on the disabled list.
Cody Ross brings some pop to the outfield, and Ryan Sweeney -- who came over in the Andrew Bailey trade -- brings a solid glove and a line-drive stroke which might thrive at Fenway.
From the mound, the Sox come at teams with a 1-2-3 punch of Jon Lester, Beckett and Clay Buchholz, who seems to be over the back woes that ruined his 2011 season.
Lester, who could be in position for that breakout season after several years of solid work, will try to set the tone a little better than he did last year in Arlington, Texas.
"I have the experience of knowing what to expect," Lester said. "I think there's a learning curve to pitch Opening Day that a lot of people don't understand. It's just something that you have to experience to get better at. Hopefully, this year will go a little better than last year."
As always, Opening Day represents a chance for rebirth.
"I think our individual players are much different than what the perceptions of September of 2011 were," Cherington said. "I think they are motivated to go show people that. So that's what I'm looking forward to, more than anything else."