The development of the vascular tree during embryogenesis involves vasculogenesis, angiogenesis and tissue-specific differentiation of endothelium which gives rise to many different vessel types. These processes are physiological complex and are therefore difficult to study in vitro. However, the discovery of endothelial cell-specific receptors and cognate ligands has led to the generation of transgenic and knockout mouse models which have shed light on the molecular mechanisms that regulate the development of blood and lymphatic vessels during embryogenesis. Such mouse models have demonstrated that members of the vascular endothelial growth factor (VEGF) family of proteins and the VEGF receptors are critical regulators of vasculogenesis, angiogenesis and endothelial cell differentiation. The availability of purified VEGF family members and of inhibitors of these growth factors may provide a means to modulate blood vessel growth for the treatment of cancer, retinopathies and diseases of ischemia.