Due to its immunogenecity and evidence of immune responses resulting in tumor regression, metastatic melanoma has been the target for numerous immunotherapeutic approaches. Unfortunately, based on the clinical outcomes, even the successful induction of tumor-specific responses does not correlate with efficacy. Immunotherapies can be divided into antigen-specific approaches, which seek to induce T cells specific to one or several known tumor associated antigens (TAA), or with antigen-nonspecific approaches, which generally activate T cells to become nonspecifically lytic effectors. Here the authors critically review the different immunotherapeutic approaches in melanoma.