Vascularization of organs and tissues proceeds by either of two distinct processes, angiogenesis or vasculogenesis (l). The first vascular structures in the embryo, such as the heart or the dorsal aorta, are formed by vasculogenesis, ie the de ttovo formation of blood vessels from differentiating endothe-lial cell precursors, or angioblasts. Angiogenesis, the sprout-ing of capillaries from pre-existing blood vessels, further refines the primitive embryonic vascular system and is the principal process, by which certain organs, such as the brain or the kidney, are vascularized. Unlike vasculogenesis, which is apparently restricted to embryonic vascular development, angiogenesis occurs also during certain physiological processes in the adult organism, for example during the female reproductive cycle, during pregnarcl, or during wound healing. Furthernore, angiogenesis plays a major role in the pathogenesis of angiogenesis-dependent diseases, such as diabetic retinopathy or retinopathy of prematurity, psoriasis, or solid tumor growth (2). These diseases are often associated with tissue ischemia and hypoxia. Recent investigations of the molecular mechanisms underlying the regulation new blood vessel formation has focused on molecules that are involved in endothelial cell-cell or endothelial cell-extracellular matrix interactions. These include adhesive molecules, such as integrins, or angiogenic factors and their endothelial receptors-for reviews, see (3, 4). We have focused on members of two classes of endothe-lial specific receptor tyrosine kinases and their ligands, VEGF and its receptors, and the Angiopoietin-1 receptor, Tie-2. This article summarizes the role of these molecules in vascular development and in angiogenesis-dependent diseases.