A functional immune system requires a T cell repertoire that is extremely diverse so as to allow for the elimination of all possible pathogens. However, the production of an immense T cell repertoire also increases the likelihood of generating autoreactive T cells. The immune system must therefore also incorporate a means of silencing or eliminating autoreactive T cells, while minimally sacrificing T cell diversity. The induction and maintenance of T cell unresponsiveness to self antigens is thus defined as T cell tolerance. This review provides an overview of the T cell tolerance mechanisms invoked in the thymus and in the periphery to prevent the induction of autoimmunity. Factors that can influence the induction of tolerance and autoimmunity are also discussed.