Successful in both singles and doubles, he had an unusually long professional career, with many of his accomplishments coming towards the end of his career, and he is popular among spectators and other players alike for his winning demeanor and shot-making abilities; he is also one of a rare breed of player who plays two-handed on both the forehand and backhand sides.

As a singles tennis player, the 2006 Australian Open was Santoro's only Grand Slam quarterfinal appearance.

1 at some time during their careers: Novak Djokovic, Jimmy Connors, Mats Wilander, Boris Becker, Stefan Edberg, Jim Courier, Andre Agassi, Pete Sampras, Thomas Muster, Marcelo Ríos, Gustavo Kuerten, Carlos Moyá, Pat Rafter, Juan Carlos Ferrero, Marat Safin, Lleyton Hewitt, Andy Roddick, and Roger Federer (against whom he has a 2–9 record).

1 players, Santoro is 0–6 against Yevgeny Kafelnikov, 0–1 against Ivan Lendl, 0–1 against Rafael Nadal, and 0–2 against Andy Murray.

In addition to his doubles prowess, Fabrice is noted for his cheery attitude on court and his vast arsenal of trick shots, making him a crowd favorite and gaining him the admiration of his peers.

In recognition of Santoro's varied and innovative style of play, Pete Sampras has nicknamed him The Magician.

With his participation in the 2008 Australian Open, he broke Andre Agassi's record in Grand Slam appearances over his career with a total of 62.

Santoro retired at the end of the 2009 season at his hometown tournament at the 2009 BNP Paribas Masters in Paris (Bercy), losing his final singles match against James Blake and final doubles match against Johan Brunström and Jean-Julien Rojer while partnering with compatriot Sébastien Grosjean.

According to the ATP website, as of the 2019 Davis Cup Finals, Feliciano López has lost more singles matches (475) than any other professional player (active or not), surpassing the record previously held by Santoro.