Vascular endothelial growth factors (VEGFs) are a family of secreted polypeptides with a highly conserved receptor-binding cystine-knot structure similar to that of the platelet-derived growth factors. VEGF-A, the founding member of the family, is highly conserved between animals as evolutionarily distant as fish and mammals. In vertebrates, VEGFs act through a family of cognate receptor kinases in endothelial cells to stimulate blood-vessel formation. VEGF-A has important roles in mammalian vascular development and in diseases involving abnormal growth of blood vessels; other VEGFs are also involved in the development of lymphatic vessels and disease-related angiogenesis. Invertebrate homologs of VEGFs and VEGF receptors have been identified in fly, nematode and jellyfish, where they function in developmental cell migration and neurogenesis. The existence of VEGF-like molecules and their receptors in simple invertebrates without a vascular system indicates that this family of growth factors emerged at a very early stage in the evolution of multicellular organisms to mediate primordial developmental functions.