Defects in T cell homeostatic mechanisms can result in T cell lymphopenia, defined as decreased numbers of lymphocytes. Lymphopenia results in homeostatic proliferation in order to maintain T cell homeostasis. It has been proposed that homeostatic proliferation can expand the pool of autoreactive T cells that promote autoimmunity, and indeed recent studies have further substantiated this observation in both animal models and humans. Conversely, homeostatic proliferation can promote tumor immunity by allowing tumor-specific T cells to accumulate. In this review, we discuss how the outcome of homeostatic proliferation can function both in a deleterious manner in autoimmunity and a beneficial way in tumor immunity. We also discuss the roles of various cytokines and T regulatory cells that control homeostatic proliferation.