Epidemiologic data demonstrate sex differences in autoimmune diseases, immune responses against infection, and antitumor immunity, and accumulating evidence suggests a major role for sex hormones in mediating these differences. In this study, we review recent advances in understanding how sex hormones regulate T cell responses to alter susceptibility to autoimmunity. Although sex hormones can directly alter gene transcriptional programs of T cells, we focus in this study on how sex hormones alter T cell development and function through their effects on thymic stromal cells and innate cell types. In addition to contributing to our understanding of sex differences, these findings also have implications for the therapeutic use of sex hormones and sex hormone modulators, which are now being prescribed to increasing numbers of patients for a wide variety of indications.