Management of malignant melanoma continues to present a challenge to dermatologists, particularly in advanced cases. In light of the steady increase in the worldwide incidence and mortality rates for melanoma, better understanding of the immune mechanisms regulating melanoma progression and interaction with the host’s immune system seems eminently important. New studies on the role of immune mechanisms in the pathogenesis and clinical course of melanoma have recently been published. We review the immune mechanisms involved in tumor progression and ways in which these mechanisms may be applied toward immunotherapeutic management of malignant melanoma. (J Am Acad Dermatol 2000;43:167-85.) Learning Objective: After the completion of this learning activity, participants should be familiar with (1) the immune mechanisms involved in host-tumor interaction and tumor rejection, (2) factors allowing the escape of melanoma cells from immune recognition, and (3) the current rationale for the different types of specific immunotherapy in melanoma. Better understanding of basic mechanisms in tumor immunology should raise awareness of future immunotherapeutic approaches in patients with melanoma, particularly in those who are at high risk of recurrence or who present with advanced disease.