An extensive literature base documents the substantial incremental prognostic value of nuclear cardiology compared with information provided by risk factors, clinical history, electrocardiographic stress testing results, and coronary arteriography. A smaller, well-established and growing literature addresses the unique potential of nuclear cardiology to assess therapeutic response of ischemic heart disease to lifestyle and medical therapies in individual patients. General guidelines focus on management of individual risk factors based on large studies, but may not reflect the optimum treatment strategy for an individual patient. The central rationale for noninvasive serial monitoring is to optimize the effectiveness and timing of lifestyle, medical, and revascularization therapies to minimize coronary event risk. Ideally, this monitoring of therapy should be early in the management of coronary artery disease (CAD) and guide the need for more intensive therapeutics. The application of technical advances in serial monitoring has the potential to revolutionize the way we diagnose and prevent CAD, even in asymptomatic patients. The potential long-term cost effectiveness of positron emission tomography and single-photon emission CT myocardial perfusion scintigraphy in detecting and monitoring treatment of CAD offers great promise for reducing coronary events in known or suspected ischemic heart disease.