A balance between an adequate immune response to an antigen or pathogen and tolerance is a prerequisite for normal immune homeostasis and the well-being of the host. In this complex self-regulation, multiple mechanisms have been implicated as contributing to the immune tolerance network, including apoptosis, anergy, and active suppression. Current excitement focuses on active suppression and new regulatory T cell-mediated pathways of immunosuppression that are being unraveled. Central to several of these pathways is transforming growth factor-beta (TGF-beta), a potent immunoregulatory cytokine that contributes to the function and generation of regulatory T cells.