At the Mutua Madrileña Madrid Open, Rezaï caused a huge upset in the first round, defeating the former world No. 1 and four-time French Open champion Justine Henin 4–6, 7–5, 6–0. In the second round, she won her match against Klára Zakopalová 6–3, 7–5, then defeated Andrea Petkovic in two sets 6–4, 7–6 (10–8). Rezaï pulled off a major fourth-round upset by defeating Jelena Janković in two straight sets 7–5, 6–4. In the semifinal she won against Lucie Šafářová (6–1, ret.) reaching the most important final in her career. She defeated Venus Williams in the final 6–2, 7–5, coming back from a 2–5 deficit and overcoming numerous set points to win. She then to the French Open with improved odds. Because of her performance at Mutua Madrileña, Rezaï reached a new high career ranking as No. 16. Seeded 15th at the French Open, Rezaï fell to No. 19 Nadia Petrova in the third round in three sets.