See main article: 2006 NASDAQ-100 Open.
Defending champion Roger Federer defeated Ivan Ljubičić in the final, 7–6(7–5), 7–6(7–4), 7–6(8–6) to win the men's singles tennis title at the 2006 Miami Open. With the win, Federer achieved his second Sunshine Double (following 2005).
All seeded players receive a bye into the second round.