Positron emission tomography (PET) is an intrinsically quantitative tool that provides a unique and unparalleled approach for clinicians and researchers to interrogate the heart noninvasively. The ability to label substances of physiological interest with positron-emitting radioisotopes has permitted insight into normal blood flow and metabolism and the alterations that occur with disease states. The efficacies of interventional therapies also have been demonstrated with cardiac PET. PET is unequaled in establishing the presence or absence of coronary artery disease (CAD) as well as for assessment of myocardial viability. Using mathematically and physiologically appropriate models, myocardial blood flow, metabolism, and ligand density and flux can be measured noninvasively, providing physicians and researchers with an exceptional window to the heart. Future advances in both instrumentation as well as radiochemistry and image processing will improve our understanding of the heart under normal conditions as well as with disease and should provide therapeutic approaches to enhancing the treatment of patients with heart disease of diverse etiologies.