In his career thus far he has won 75 men's doubles titles, including a gold medal at the 2000 Summer Olympics, the ATP World Tour Finals 4 times, and 7 Grand Slam men's doubles titles. In addition, Nestor won the 2007 Australian Open mixed doubles title with Elena Likhovtseva. This pairing also reached the finals of the 2006 Australian Open and the 2006 French Open. Nestor also won the 2011 Australian Open mixed doubles title with Katarina Srebotnik. In June 2011, he captured the 2011 French Open men's doubles title with Max Mirnyi.

He won three Grand Slam doubles titles together with longtime partner Mark Knowles of the Bahamas. The tandem won the 2002 Australian Open, the 2004 U.S. Open and the 2007 French Open. He and Knowles also reached the final of the 1995 Australian Open, the 1998 French Open and U.S. Open, the 2002 French Open and Wimbledon, the 2003 Australian Open and the 2005 Wimbledon He became the no. 1 ranked doubles player in the world in August, 2002. Nestor's career-high singles ranking is world no. 58, which he reached in August, 1999. In mixed doubles, he reached the 2003 U.S. Open final and the 2006 Australian Open final, as well as winning the mixed doubles event at the 2007 Australian Open with partner Elena Likhovtseva and the 2011 Australian Open with Katarina Srebotnik.

In 2011, he won four titles with Mirnyi: the French Open, Memphis, the Shanghai Masters and the Year End Championships in London. In the final of the Year End Championships, he played his 1,148th match, an all-time record.