They won two World Series with him. They haven't been back to the World Series since they traded him away.
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And while it's wrong to suggest that Manny was the only thing the Red Sox were missing the last 2 ½ years, it's just as wrong to think that they were the same team without the force he represented in the middle of the lineup.
This is supposed to be the year the Red Sox make it back. And Adrian Gonzalez is supposed to be that force.
And sure enough, on the day that Ramirez left baseball in disgrace, Gonzalez played a big part in Boston's long-delayed first win of the season ... by bunting for a hit to start a two-run rally that helped the Sox hold onto their 9-6 win over the Yankees.
Manny punted. Adrian bunted.
Hey, no one said Adrian had to be Manny. But no one really expected him to bunt, either.
"I don't know if you guys have watched, but I've put plenty of bunts down when they play that shift," Gonzalez said.
He's right, apparently. I know, because I checked with CBSSports.com colleague Scott Miller, who lives in San Diego and watches a whole lot more Padre games than anyone else I know.
Gonzalez is learning quickly that playing for the Red Sox is different from playing for the Padres. He's learning, because here every game is the end of the world, and here an 0-6 start to the season is a crisis.
Friday was a strange day at Fenway, even before the news circulated (right about the time Gonzalez bunted for his hit) that Ramirez was retiring rather than face another drug suspension. It was strange, because this Red Sox team was never supposed to be 0-6.
It was strange, because Red Sox general manager Theo Epstein felt the need to speak in a pregame clubhouse meeting.
"Everyone was like, 'Wow!'" David Ortiz said. "Especially the guys who really know him. That was motivation."
Ortiz said Epstein told the Red Sox that he believes in them. He may have lifted a little pressure off a team that could have been feeling it, a team forced into two roster moves before the home season began (sparing Dennys Reyes, who was designated from assignment, a probable dose of booing from the Fenway fans).
There is pressure here, which is why manager Terry Francona could say after Friday's win, "I've never seen a team so happy to be 1-6."
There is pressure, and that may be one reason why Carl Crawford, the other big Red Sox acquisition, is off to a .143 start.
There is pressure, but Gonzalez seems not to be affected by it.
"I never see anything as pressure, because whether you go 0-for-4 or 4-for-4 you're going to have fun," he said.
Maybe this guy is more like Manny than we thought.
No, they're not the same. There will be no stories about Adrian being Adrian.
But Ramirez performed in Boston, in part because he never saw anything as pressure, either.
It was Ramirez who famously said when the Red Sox were down to the Indians in the 2007 playoffs, "If it doesn't happen, who cares? It's not like it's the end of the world."
And it was Gonzalez who said Friday, after the first Red Sox win of the season, that he didn't even see an 0-6 start as pressure.
"Why?" he said. "If we're doing the best we can, that's all we can do. Baseball's not always going to go your way."
The Red Sox need Gonzalez to perform every bit as much as they once needed Ramirez to perform. Maybe more, because there continue to be real questions about whether this team's rotation is good enough.
John Lackey was terrible again on Friday, although by lasting five innings (giving up at least one run in each), he outdid Phil Hughes and actually got statistical credit for the win. Lackey has a 15.58 ERA through two starts, but there has to be concern about Josh Beckett and Daisuke Matsuzaka as well.
The idea is that the Red Sox bullpen will work as it did Friday, when Alfredo Aceves joined the trio of Bobby Jenks, Daniel Bard and Jonathan Papelbon to provide four innings of one-hit, scoreless relief.
But the idea is also that an offense centered in part around Gonzalez will have a lot of days like Friday, days when the starting pitcher doesn't need to be the story.
The idea is that Gonzalez is the perfect hitter for Fenway Park, a ballpark he had never played in before Friday.
He's heard it.
"Too many [times]," Gonzalez said. "Let me play, and you guys can write whatever happens."
That works. Here's what happened Friday:
Manny punted. Adrian bunted.
And the Red Sox won.