Worldwide incidence of malignant melanoma has been constantly increasing during the last years. Surgical excision is effective when primary tumors are thin with thickness of less than 1milli meter and there is no evidence of metastases. At later disease stages patients often succumb, due to failure of metastasis control. Therefore, great efforts have been made to develop improved strategies to treat metastatic melanoma patients. In the search for novel treatments during the last two decades, immunotherapy has occupied a prominent place. Numerous early phase immunotherapy clinical trials, generally involving small numbers of patients each time, have been reported; significant tumor-specific immune responses could often be measured in patients upon treatments. However, clinical responses remain at a dismal low rate. In some cases, objective clinical benefit was more frequently observed among immune responders than immune non-responders. This clearly calls for a better understanding of protective immunity against tumors as well as the cross talk taking place between tumors and the immune system. Here we discuss advances and limitations of specific immunotherapy against metastatic malignant melanoma in the light of the literature.