Several clinical trials of therapeutic angiogenesis in patients with coronary artery disease have shown clinical improvement and provided some objective evidence of improved perfusion and left ventricular function. Larger-scale, placebo-controlled trials, as well as studies of combinations of growth factors and the use of endothelial progenitor-cell or stem-cell supplementation, are in progress. Revascularization of ischemic myocardium with angiogenic compounds and without the mechanical manipulation of atherosclerotic vessels has great potential in the treatment of coronary artery disease. If it is proven to be both safe and efficacious, the revascularization of tissue biologically via medical or gene therapy will be a major advance in the treatment of patients with a diffuse disease that is not amenable to conventional therapy and in the augmentation of revascularization in patients undergoing traditional surgical therapies.