He played in Major League Baseball (MLB) for the San Diego Padres, Cincinnati Reds, Cleveland Indians.

He also played in Nippon Professional Baseball (NPB) for the Fukuoka SoftBank Hawks and in the KBO League for the Samsung Lions and the KT Wiz.

Germano made his major league debut with the San Diego Padres on May 22, 2004, getting the win as the starting pitcher against the Philadelphia Phillies.

On July 23, 2005, Germano and Travis Chick were traded to the Cincinnati Reds in exchange for Joe Randa.

He made 8 starts down the stretch for the Triple–A Louisville Bats, posting a 3–2 record and 4.01 ERA with 38 strikeouts across 49+2⁄3 innings pitched.

Germano is the first ever MLB pitcher to throw a major league pitch in China, starting for an exhibition game as the Padres starter against the Los Angeles Dodgers.

In September it was revealed that Germano had been pitching with an inflamed Achilles tendon, and was knocked out for the rest of the season and the playoffs.

[1] On July 30, Germano was called up by the Cleveland Indians to join their bullpen ahead of the team's upcoming game against the Toronto Blue Jays.

On July 3, after he exercised his opt-out clause, Germano was called up to the majors to replace Clayton Mortensen, who was optioned to the minors earlier in the day.

[4] Germano signed a minor league deal with a Spring training invitation with the Blue Jays on November 9, 2012.

[6] He appeared in one game with Toronto before being designated for assignment on May 3 to make room for Ricky Romero on the 25 man roster.

On December 18, 2013, Germano signed a minor league contract with the Texas Rangers with an invite to spring training.