Transforming growth factor beta (TGFβ) controls numerous cellular responses, including proliferation, differentiation, apoptosis and migration. This cytokine is produced by many different cell types and has been implicated in the pathogenesis of many diseases, ranging from autoimmune disorders and infectious diseases to fibrosis and cancer. However, TGFβ is always produced as an inactive complex that must be activated to enable binding to its receptor and subsequent function. Recent evidence highlights a crucial role for members of the integrin receptor family in controlling the activation of TGFβ. These pathways are important in human health and disease, and new insights into the biochemical mechanisms that allow integrins to control TGFβ activation could prove useful in the design of therapeutics.