He remained the highest-selected player drafted directly from a Puerto Rico high school until 2012, when Carlos Correa became the first overall pick.

In 2004 Rodríguez was gone, giving Castro his first opportunity as a starter but a .135 batting average and an early-June season-ending injury finished his time in Florida.

Castro is known as a good defensive catcher, but, despite showing occasional home run power has never displayed sufficient hitting skills to win a job as a starter, along with struggling with injuries throughout his career.

In 2005, he was backup catcher to Mike Piazza, with 41 RBIs in 209 at-bats, a career-best .244 batting average, and playing solid defense.

It was most likely due to his injury-riddled career, which became evident once more when he strained his hamstring late in spring training that year, missing the beginning of the season.

On May 29, 2009, Ramon was traded to the Chicago White Sox for pitcher Lance Broadway after Omir Santos won the backup job with the return of Brian Schneider from the DL.

On July 23, 2009, Castro became the 17th backstop in Major League Baseball history to catch a perfect game, receiving Mark Buehrle's second no-hitter.