Improved treatment options and better management of cardiovascular risk factors have resulted in improved outcomes for patients suffering from severe coronary artery disease. However, coronary artery disease may be of such a diffuse and severe manner that repeated attempts at catheter-based interventions and coronary artery bypass grafting may be unsuccessful at restoring normal myocardial blood flow. It is the goal of therapeutic angiogenesis to restore perfusion to chronically ischemic myocardium using protein growth factors, gene therapy, or, more recently, cell-based therapy, without intervening on the epicardial coronary arteries. However, angiogenesis has not yet provided significant clinical benefit and is still reserved as an experimental treatment for patients who have failed conventional therapies. Once potential endogenous inhibitors of vascular development can be modified, angiogenesis may become more useful for therapeutic purposes. It is hoped that angiogenesis for therapeutic purposes will one day effectively re-create the potent natural processes of vascularization that every human being undergoes during growth and development and become a major modality for the treatment of coronary artery disease.