Of all malignancies, melanoma has the most rapid increase in incidence; in 2009 it was estimated to have had the fifth highest number of new cases overall. Surgical therapy remains the primary and most effective intervention for this disease. Over the past 20 years there has been a significant paradigm shift in the management of the regional nodal basin, driven predominantly by the introduction of sentinel lymph node biopsy (SLNB). This new technique has drastically altered the method of detecting nodal disease and has become a routine component of melanoma treatment. In addition to SLNB, a better understanding of ultrasound, fine-needle biopsy, and the considerable efforts to minimize the morbidity of surgical intervention has led to innovations in the management of patients with regional metastases. An overview of the current therapeutic options for managing patients with nodal disease follows.