The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy for melanoma has emerged during the last 2 decades as a minimally invasive approach to evaluate regional lymph node basins in patients with intermediate- and high-risk primary cutaneous melanoma and has changed our approach to the clinically negative lymph node basin in melanoma during the same period. This review focuses on preoperative assessment and operative strategies, pathologic evaluation of the SLN, issues related to regional lymph node basin control, and current clinical practice guidelines. Predictors of SLN status, the prognostic significance of the SLN, and areas of controversy are also discussed.