Angiogenic molecules are the focus of therapeutic efforts to promote new vessel development in ischemic or damaged tissue and, conversely, to inhibit endothelial cell growth and survival in proliferative disease. Two novel angiogenic mitogens have been characterized recently. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and the mammalian homologue of Bombina variegata peptide 8 (Bv8) are endothelial cell mitogens and chemotactic factors with restricted expression profiles and selective endothelial cell activity. These highly related peptides share two cognate G-protein-coupled receptors that are homologous to the neuropeptide Y receptor. The identification of tissue-selective angiogenic factors raises the possibility that other secreted molecules in this class exist. The potential advantage of tissue-specific angiogenic therapeutics may be the reduction of systemic side effects. Additionally, these peptides or their receptors may be attractive targets for inhibition in several disorders.