Positron Emission Tomography (PET) is the only available technique that permits quantification of regional myocardial perfusion in humans. To this end, tracer kinetic models and appropriate tracers such as 13N-Ammonia and 15O labeled water are required. Quantification is possible because accurate radioactivity quantities can be measured externally, both for the vascular and myocardial compartments. Normal value for baseline and maximal perfusion after pharmacologically induced vasodilatation of the resistance microcirculatory vessels are age-dependent. The functional hemodynamic significance of epicardial stenoses can be estimated from the progressive reduction in coronary perfusion reserve, which decreases progressively when stenosis severity reaches 40% in diameter. The effect of revascularization procedures such as CABG and PTCA can be objectively measured. In addition, there is increasing evidence from PET studies that resistive vessel dysfunction (probably through endothelial factors) contributes to the reduced perfusion reserve in patients with epicardial coronary artery disease. Therefore quantification of myocardial perfusion with PET appears an ideally suited endpoint for primary and secondary prevention trials.