Angiogenic cytokines constitute a potentially novel form of therapy for patients with cardiovascular disease. The feasibility of using recombinant formulations of angiogenic growth factors to expedite and/or augment collateral artery development in animal models of myocardial and hindlimb ischemia--'therapeutic angiogenesis'--has now been well established. These studies have suggested that two angiogenic growth factors in particular--basic fibroblast growth factor and vascular endothelial growth factor--are sufficiently potent to merit further investigation. More recently, experiments performed in our laboratory have indicated that, in the case of vascular endothelial growth factor--a secreted protein--similar results may be achieved by percutaneous arterial gene transfer. Further laboratory and clinical studies may yield promising insights into the fundamental basis for native as well as therapeutic angiogenesis, and at the same time more explicitly define the manner in which therapeutic angiogenesis may be successfully incorporated into clinical practice.