Surgical excision, alone or in combination with chemotherapy, has gained increasing support in both the surgical and the medical oncology fields over the last two decades. The general principles governing surgical decision making relies upon the ability to remove all active disease or control severe symptoms. Frequently, a trial period of chemotherapy will permit a reduction in the volume of metastatic disease as well as provide a window into the clinical behavior of the tumor. Rapid progression of disease to areas outside the proposed resection field indicates the probable futility of resection strategies and are not indicative of a missed opportunity for surgical intervention. When complete resection is possible, the use of effective adjuvant chemotherapy should be considered, if available For patients with extensive extremity involvement with satellite or in-transit melanoma, results of isolation perfusion have been consistent across multiple series. Complete response rates above 50% are routinely achieved, with long-term (5 years) limb salvage achieved in approximately 20% of patients. The extent of tumor burden does and the addition of Tumor Necrosis Factor-a (TNF) do not appear to impact on response or response duration. Repeated perfusion is possible with results mirroring that achieved during the primary perfusion. At the time of operative dissection, complete dissection of the lymph node basin associated with the cannulated vessels is routinely performed. Our practice is to obtain vascular access at the most distal location which ensures all diseases will be within the perfusion distribution, preserving more proximal access points for potential future use. The use of prophylactic limb perfusion for patients with high-risk primary tumors has not been associated with a survival benefit and is not recommended.