Multicenter clinical trials have established new standards of care in the surgical and medical management of malignant melanoma. They have led to the testing of new therapies and improved outcomes for patients with loco-regional and distant disease. Many pressing questions remain, however, and additional multicenter trials are currently underway to address them. The purpose of this review is to summarize relevant ongoing and planned multicenter trials that have and continue to define current melanoma management. J. Surg. Oncol. 2011; 104:430–437. © 2011 Wiley-Liss, Inc.