Interactions between vascular endothelial cells (EC) and materials are central to biomedical applications such as vascular graft endothelialization or vascularization of an engineered tissue substitute. To improve implant success, biomaterial surfaces are designed to modulate EC adhesion and responses. In vivo, EC line all blood vessels; their morphology, function and associated matrix are adapted to and specific for the local microenvironment. To enhance EC adhesion and growth, surface treatments have been developed that modify material surface physico-chemical and mechanical properties. Materials may also be coated with bioactive molecules such as proteins from the matrix, peptides and/or growth factors to study and control EC behaviour. The aim of this review is therefore to give an overview of current knowledge related to EC and their matrix environment in vivo and their responses to synthetic surfaces in vitro.