Positron emission tomography is an intrinsically quantitative tool which permits the quantitative assessment (i.e., in ml/g/min) of regional myocardial perfusion. Oxygen-15-labeled water is the only positron-emitting flow tracer which is freely diffusible within the myocardium. It has been used extensively to define normal myocardial perfusion physiology, as well as to delineate the effects of numerous cardiac diseases on myocardial perfusion and to assess the efficacy of therapeutic interventions. This brief review summarizes the major observations that have been made in humans using oxygen-15 water and positron emission tomography for quantitative estimation of regional myocardial perfusion.