PET provides robust and reproducible measurements of regional myocardial blood flow in milliliters per minute per gram of tissue, providing unique pathophysiologic and diagnostic information on the function of the coronary macro- and microcirculation. There is compelling evidence to suggest that in many instances abnormalities of global myocardial perfusion are demonstrated in individuals with either coronary risk factors for coronary artery disease or different myocardial diseases in the absence of angiographically demonstrable stenosis of the epicardial coronary arteries. In this context, measurement of myocardial blood flow gives unique diagnostic information regarding the function of the coronary microcirculation and provides a quantitative surrogate endpoint against which the efficacy of treatments can be established.