Cytotoxic T-cells can recognize antigens that are presented on the surface of human tumor cells and thereby mediate cancer regression. Importantly, those immune interventions that have thus far proven most successful in the clinic-i.e. checkpoint blockade and tumor-infiltrating lymphocyte (TIL) therapy-enhance T-cell activity without a deliberate focus on specific antigens. Thus, one major question remains unsolved: what is the nature of the antigens that need to be recognized on human cancer to result in tumor control? Here we discuss the repertoire of human tumor antigens by three main parameters. Firstly, the extent to which these antigens are shared by larger patient groups; secondly, the degree of tumor-restrictive expression; and finally, the likelihood of antigen loss the moment selection pressure is applied. Using this framework, we describe those classes of antigens that can be considered preferable targets in both active and passive T-cell based cancer immunotherapy.