Vascular endothelial growth factor (VEGF) is a key molecule that orchestrates the formation and function of vascular networks. Impaired regulation of angiogenesis is implicated in a number of pathologic states. For instance, neoplasias exhibit uncontrolled angiogenesis, whereas ischemia and states of vascular insufficiency involve reduced VEGF activity. As the role of VEGF has been elucidated in these disease processes, its therapeutic role has been developed. The Food and Drug Administration has approved several anti-VEGF agents for treating colorectal, lung, and kidney cancer. VEGF-inducing agents have also been used experimentally to induce angiogenesis in patients with critical limb ischemia. As more knowledge is gathered about the biology of VEGF and its receptors, there is greater promise for therapeutic modulation of VEGF expression. The purpose of this review is to describe the various therapeutic and biologic factors that regulate the expression of VEGF.