Locally advanced melanoma is characterized clinically by the appearance of in-transit or satellite metastases, and is considered stage IIIB or IIIC according to the 2002 classification of the American Joint Committee on Cancer. Despite the absence of distant metastases, the management of locally advanced melanoma is complicated and the disease is associated with a reduction in overall survival. The initial step in the approach to the patient with locally advanced melanoma involves the restaging in order to exclude the presence of distant metastases. Positron emission tomography-computed tomography is currently accepted as the most accurate restaging technique. Surgical excision of the metastases continues to be the treatment of choice for locally advanced melanoma. In the case of unresectable metastases, hyperthermic isolated limb perfusion with melphalan with or without tumor necrosis factor has achieved complete responses in up to 60% of patients treated, with very rare severe locoregional and systemic toxic effects. Radiation therapy, chemotherapy, and biochemotherapy are options that, even though they have not been tested in patients with only in-transit metastases, may have a role in unresectable, locally advanced melanoma without distant metastases.In any case, therapeutic options for locally advanced melanoma should be individualized, and should take into consideration the availability of each of these techniques as well as the experience of the health care team.