The ability of the coronary circulation to autoregulate is essential for the heart to respond to metabolic demands. Several alterations in function may limit maximal coronary perfusion including atherosclerosis, structural abnormalities of small coronary vessels, extravascular compressive forces, thrombosis, abnormal endothelial regulatory function, and the effect of abnormal myocardium on the coronary circulation. Coronary flow reserve is a unifying concept that examines the limitation in myocardial perfusion that certain disease states impose. At present, even with state-of-the-art technology, the measurement of coronary flow reserve is difficult in routine clinical situations. As the ability to measure regional myocardial perfusion improves, coronary flow reserve may gain more widespread clinical use with perhaps as yet undiscovered therapeutic implications.