Melanoma is often evaluated for the development of anticancer immunotherapeutics. Fascinating immune and clinical responses in small numbers of patients have prompted various approaches, ranging from nonspecific immune stimulation to therapies that target specific antigens. Unfortunately, these immune therapies have often shown limited success and objective responses have been seen in only a modest subset of patients. The challenge has been to identify factors that can lead to more consistent clinical benefit and to develop strategies to overcome the obstacles to successful antitumor immunity. Over the last 15 years many immune targets have been identified in cancers and the mechanisms underpinning clinical responses have become better understood. Furthermore, new ways to manipulate anticancer immunity are making it possible to overcome cancer immune evasion and subversion. New therapeutic strategies are resulting from these emerging insights into the relationship between melanoma and the host immune response.