Over the last 30 years, considerable progress has been made in drug therapy for chronic ischemic heart disease (IHD). Most pharmacologic therapies act by reducing myocardial oxygen consumption, increasing coronary blood flow, improving ventricular relaxation, dilating collateral vessels, and reducing peripheral resistances. Despite "optimal" medical therapy, a large fraction of patients continue to present with angina and myocardial ischemia. Coronary angioplasty (percutaneous transluminal coronary angioplasty) may improve symptoms, but several subgroups of patients, including the elderly, or those who have diabetes mellitus or heart failure, represent high-risk populations that do not always benefit from coronary revascularization. Epidemiologic studies show that life expectancy is longer compared with previous decades and that the prevalence of diabetes is increasing sharply worldwide. In addition, the prevalence of heart failure is growing because of the decreased death rate from acute myocardial infarction and improved survival of patients who have undergone coronary revascularization. We focus on this changing scenario of chronic IHD and propose an innovative approach to the treatment of angina in this context.