Rodríguez was selected with the 27th pick in the first round, by the Phoenix Suns, in the 2006 NBA draft (and later that day traded to the Portland Trail Blazers in exchange for cash considerations).

On July 20, 2006, it was announced that the Trail Blazers had negotiated a buyout with his Spanish League club Estudiantes, and signed him to an NBA rookie-scale contract.

[5] Retrospectively, McMillan shared the opinion that Rodríguez had entered the NBA "too young", allegedly undeveloped as player.

On July 5, 2010, after spending four seasons in the NBA, Rodríguez signed a 3-year contract with the Spanish team Real Madrid.

[12] In the 2014–15 season, Real Madrid won the EuroLeague, after defeating Olympiacos, by a score of 78–59 in the 2015 finals game.

[15] He made his debut for the 76ers in their season opener on 26 October 2016, recording 12 points and nine assists in a 103–97 loss to the Oklahoma City Thunder.

[18] On July 12, 2019, Rodriguez signed a three-year deal with the Italian basketball team, Pallacanestro Olimpia Milano.

[20] On July 2, 2022, Rodriguez amicably parted ways with the Italian club after three seasons, having also served as the team's captain.

In August 2006, Rodríguez won the gold medal at the 2006 FIBA World Championship, while playing with the senior men's Spain national team.

An adept to pick and roll plays and with a flair for passing,[25] Rodríguez has mastered the art of feeding athletic big-men and small-forwards with alley-oops.