Strict control of T-cell homeostasis is required to permit normal immune responses and prevent undesirable self-targeted responses. Transforming growth factor-beta (TGF-beta) has been shown to have an essential role in that regulation. Owing to its broad expression, and inhibitory effects on multiple cell types of the immune system, TGF-beta regulation is complex. Through advances in cell-specific targeting of TGF-beta signalling in vivo, the role of TGF-beta in T-cell regulation has become clearer. Recent in vitro studies provide a better understanding of how TGF-beta regulates T-cell homeostasis, through multiple mechanisms involving numerous cell types.