Harnessing T-cell responses to constrain tumor growth is a realistic treatment aspiration in tumor medicine, as many tumors express specific tumor associated antigens that are recognized by the adaptive immune system. CD8 T cells have direct cytolytic activity against tumor cells, and CD4 T cells mount a variety of responses that have important influences on tumor growth. We discuss how individual T-cell subsets contribute to antitumor responses and the goals and problems associated with generating and/or maintaining effective multifunctional T-cell responses to provide long-term protection against tumors.