Syndecans are heparan sulphate proteoglycans consisting of a type I transmembrane core protein modified by heparan sulphate and sometimes chondroitin sulphate chains. They are major proteoglycans of many organs including the vasculature, along with glypicans and matrix proteoglycans. Heparan sulphate chains have potential to interact with a wide array of ligands, including many growth factors, cytokines, chemokines and extracellular matrix molecules relevant to growth regulation in vascular repair, hypoxia, angiogenesis and immune cell function. This is consistent with the phenotypes of syndecan knock-out mice, which while viable and fertile, show deficits in tissue repair. Furthermore, there are potentially important changes in syndecan distribution and function described in a variety of human vascular diseases. The purpose of this review is to describe syndecan structure and function, consider the role of syndecan core proteins in transmembrane signalling and also their roles as co-receptors with other major classes of cell surface molecules. Current debates include potential redundancy between syndecan family members, the significance of multiple heparan sulphate interactions, regulation of the cytoskeleton and cell behaviour and the switch between promoter and inhibitor of important cell functions, resulting from protease-mediated shedding of syndecan ectodomains.