The last few years have witnessed the publication of a large body of evidence demonstrating conclusively the existence of tumor-associated antigens. A large majority of these studies focused on melanoma-associated tumor antigens because of the collective evidence that the immune system can influence the pathogenesis of melanoma, and because of the well-documented, although limited, success of immunotherapeutic modalities in melanoma patients. This review summarizes what is known about melanoma-associated antigenic peptides: their identity, presentation by human leukocyte antigen class I molecules to cognate T cell receptors, and their potential to induce an effective immune response. The inability of melanoma patients to mount an efficacious antitumor response and the distinction between antigenicity (i.e., the ability to express a tumor antigen) and immunogenicity (i.e., the ability to elicit an effective immune response) are discussed. Recruitment of antigen-presenting cells at the tumor site is suggested as a way to overcome tumor-induced immunotolerance. The importance of developing or perfecting laboratory and/or clinical correlates of response to immunotherapeutic modalities is emphasized because of the pressing need for reliable tests that are predictive of clinical outcome.