In the immune system, transforming growth factor-β (TGFβ) affects multiple cell lineages by either promoting or opposing their differentiation, survival and proliferation. Understanding the cellular mechanisms of TGFβ-mediated regulation is complicated due to a broad distribution of TGFβ receptors on the surface of different immune-cell types. Recent studies using in vivo genetic approaches revealed a critical role for TGFβ signalling in T cells in restraining fatal autoimmune lesions. Here, we review recent advances in our understanding of a role for TGFβ signalling in the regulation of T-cell differentiation in the thymus and in the periphery, with a particular emphasis on TGFβ-mediated control of self-reactive T cells.