Transforming growth factor β (TGF‐β) is a multifunctional cytokine that regulates cell growth, differentiation, adhesion, migration and death dependent on cell type, developmental stage, or tissue conditions. Various cell types secrete TGF‐β, but always as an inactive complex. Hence, for TGF‐β to function, this latent complex must somehow be activated. Work in recent years has highlighted a critical role for members of the αv integrin family, including αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8 that are involved in TGF‐β activation in various contexts, particularly at barrier sites such as the gut, lung and skin. The integrins facilitating this context‐ and location‐specific regulation can be dysregulated in certain diseases, so are potential therapeutic targets in a number of disorders. In this review, we discuss the role of TGF‐β at these barrier sites with a focus on how integrin‐mediated TGF‐β activation regulates tissue and immune homeostasis, and how this is altered in disease.