Established modalities of treatment for obstructive coronary artery disease include medical therapy, bypass surgery and percutaneous coronary intervention. Similarly, conventional treatment of congestive heart failure is also limited to medical therapy, temporary assist devices and transplantation. A significant subset of patients with severe symptomatic coronary artery disease and end stage heart failure is not eligible for these traditional methods of treatment. In spite of maximal medical and revascularization therapy, these patients may not get adequate symptomatic benefit. After a decade of investigations, gene therapy has emerged as a promising therapeutic option for this group of patients. This review discusses newer modalities of therapy for this subset, including therapeutic angiogenesis with growth factors and cell transplantation.