Once alerted by the innate immune system to the presence of a pathogen or a cellular abnormality, the adaptive immune system responds by activating and expanding antigen-specific B and T lymphocytes. This chapter focuses specifically on the activation and activities of T lymphocytes, which coordinate the adaptive immune response. We open with a description of where and how naïve T cells first encounter antigen. We then examine what factors influence the differentiation of helper CD4+ T lymphocytes into one of several effector subsets, each of which secretes a distinct subset of cytokines. We follow with a discussion of the origin and function of cytotoxic CD8+ T cells, the lymphocyte with the capacity to directly kill tumor cells. We close with a brief summary of the unique challenges that face the adaptive immune system when it tried to mount a response to a tumor.