In singles play, Santoro defeated 18 players who were ranked world no. 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). Against other former world no. 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. Santoro is famous for his winning record against Marat Safin (7–2); Safin himself has said, "Being told I would play Santoro was being told I was to die."