Abstract Tumors, wounds, and chronic inflammatory disorders generate a new vascular supply by a process known as pathological angiogenesis. Whereas formation of the normal blood vasculature requires the interaction of many different agonists and inhibitors, including vascular endothelial growth factor-A (VEGF-A) and other members of the vascular permeability factor/VEGF family, pathological angiogenesis is a cruder, simpler process that can be replicated by a single VEGF-A isoform, VEGF-A^164/5. VEGF-A^164/5 induces the formation of several distinctly different types of new blood vessels that differ from normal blood vessels with respect to organization, structure, and function. Elucidating the properties of these new vessels has led to a better understanding of angiogenesis and will hopefully lead to new approaches to antiangiogenic therapy.