Angiogenesis is required for a variety of normal and pathological, proliferative processes. Numerous regulators of angiogenesis have been identified and characterized over the last decades. Among these, vascular endothelial growth factor (VEGF)-A appears especially important in normal development and in disease processes. Several VEGF inhibitors have been approved by the FDA for the treatment of tumors or the neovascular form of age-related macular degeneration. This article examines the molecular and biological characteristics of VEGF and also discusses preclinical and clinical studies with VEGF inhibitors and the lessons learned from these studies.