Almost 40 years ago, K. Lance Gould proposed the concept of coronary flow reserve (CFR) to quantify the effect of epicardial narrowings on myocardial blood flow (1). CFR represents the extent to which hyperemic coronary flow can increase above resting flow. These animal experiments still constitute the basis for our understanding of coronary physiology. The development of flow velocity catheters ((2),3), progress in positron emission tomography–derived absolute flow measurements (4), and, more recently, transthoracic Doppler flow velocity measurements (5) extended Gould's findings into patients with coronary artery disease. Until the description of fractional flow reserve became available ((6),7), CFR was the only index commonly used in the clinical field. Yet, the main problem with CFR in clinical practice resides in its lack of specificity for the epicardial vessel: a too-low CFR value does not determine whether this abnormal flow velocity relates to the epicardial stenosis, to microvascular disease, or to a combination of both. In addition, the cutoff value for separating normal from abnormal is actually a moving target and is influenced by a large variety of factors such as blood pressure, heart rate, resting flow (which is difficult to obtain in a patient in a catheterization or echocardiography laboratory), myocardial mass, and age.