Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context.