Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.