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Genetic studies have recently revealed a role for transforming growth factor-beta-1 (TGF-β1) and its receptors (TGF-βRs I and II as well as endoglin) in embryonic vascular assembly and in the establishment and maintenance of vessel wall integrity. The purpose of this review is threefold: first, to reassess previous studies on TGF-β and endothelium in the light of these recent findings; second, to describe some of the well-established as well as controversial issues concerning TGF-β and its regulatory role in angiogenesis; and third, to explore the notion of ‘context’ with respect to TGF-β and endothelial cell function. Although the focus of this review will be on the endothelium, other vascular wall cells are also likely to be important in the pathogenesis of the vascular lesions revealed by genetic studies.