The intracellular mechanism of transforming growth factor-β (TGFβ) signalling via kinase receptors and SMAD effectors is firmly established, but recent studies of human cardiovascular syndromes such as Marfan syndrome and pre-eclampsia have refocused attention on the importance of regulating the availability of active extracellular TGFβ. It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGFβ signalling, while soluble and membrane bound forms of TGFβ co-receptors add further layers of regulation. Together, these extracellular interactions determine the final bioavailability of TGFβ to vascular cells, and dysregulation is associated with an increasing number of vascular pathologies.