Epstein is a graduate of Yale University, majoring in American Studies, and has a law degree from the University of San Diego. After his studies, he took a job in the PR department of the San Diego Padres, and rose in that organization to be Director of Baseball Operations.
When John Henry bought the Red Sox in 2002, he appointed Epstein's former boss at the Padres, Larry Lucchino, as President and CEO. At the end of the 2002 season, Lucchino appointed Epstein to replace temporary GM Mike Port.
Under the regime of Henry, Lucchino, and Epstein, the Red Sox have stressed the dicipline of sabermetrics, the analysis of baseball through objective evidence and methods. In 2002, they hired the father of sabermetrics Bill James to be a special advisor to the team, and also hired statistical analysts such as Voros McCracken. This devotion to the new wave of talent evaluation has seen the team stress on base ability as the most important ability of a hitter, and not-so-coincidentally the 2003 Red Sox lead MLB in runs scored. They led the majors with a .289 batting average, set a team record with 238 home runs, and set a new record with a slugging percentage of .491, breaking the .489 mark of the 1927 Yankees.
Epstein's grandfather Philip Epstein and great-uncle Julius Epstein won Academy Awards for the screenplay of Casablanca.