Pitcher Craig Breslow signed a minor league contract with the Red Sox for 2006. He was named an International League (Triple-A) All-Star while with the PawSox. He was 7–1 with a 2.69 ERA and struck out an average of 10.3 batters per nine innings and named as the PawSox Most Valuable Pitcher. He was promoted to Red Sox in the second half of the season. In 13 relief appearances with the Red Sox he posted a 3.75 ERA with 12 strikeouts in 12 innings pitched.

In 2007 Breslow earned a trip to the Triple-A All-Star game in July for the second straight season for the PawSox. He was promoted to Red Sox on September 1st, but was sent back to make room on the team roster for Jon Lester. He was added to the postseason roster and has a ring from winning the 2007 World Series.

He was waived by the Sox during spring training in 2008 and claimed by the Cleveland Indians. But in July 2012, then with the Diamondbacks, he was traded back to the Red Sox. In 23 relief appearances with the Sox, he had a 2.70 ERA with 19 strikeouts and held opponents to a .206 batting average.

Breslow began the 2013 season on the disabled list with left shoulder tendinitis. He was activated on May 7th and became the Red Sox primary set-up reliever. He had a 1.81 ERA (third among left-handed relievers in the American League).

In the 2103 postseason, he pitched in 10 of 16 games, with a 2.45 ERA, and received another World Series ring. He was also named the Red Sox nominee for the "Roberto Clemente Award" that season.

Breslow began the 2014 season on the disabled list, not making his first appearance until the season's 10th game, and compiled a 5.96 ERA in 60 appearances. And again he was named the Red Sox nominee for the "Roberto Clemente Award".

In 2015 season, Breslow had one save and a 4.15 ERA and became a free agent, signing with the Marlins for 2016.

His playing career ended in 2018 and he was hired by Theo Epstein of the Cubs, to evaluate player data and development for their pitching. In 2020, he was promoted to assistant General Manager for pitching.

He was nicknamed the "smartest man in baseball" by Minneapolis Star Tribune, and The Wall Street Journal. On October 25, 2023, the Red Sox hired him as their Chief Baseball Officer.