Coronary artery disease (CAD) remains the main cause of death in the western world, despite the considerable improvements in its diagnosis and therapy in the past few decades.1 Today, CAD is widely understood to constitute an advanced stage of atherosclerosis,2 that is to say, an inflammatory pathology involving both coronary and extracoronary arteries.3 The diagnosis of CAD is frequently based on morphological observations obtained through invasive coronary angiography (ICA), whereby the presence of at least 1 coronary artery stenosis of at least 50% and a history of myocardial infarction are considered to be diagnostic. It is increasingly appreciated that perfusion imaging brings additional prognostic value compared with morphological imaging alone.4 In particular, perfusion defects can occur at any stage of atherosclerotic disease, from the earliest signs of endothelial dysfunction5,6 to the debut of nonobstructive plaques in coronary arteries,7 and in cases of intermediate or high-grade coronary artery stenoses.8 In those patients with myocardial perfusion abnormalities, individual risk for coronary events increases with the size of perfusion defects, irrespective of the nature of underlying structural or functional changes causing these perfusion defects.9 Thus, myocardial perfusion abnormalities can be understood as the functional consequence of a broad range of present atherosclerotic vessel alterations, bearing considerable significance for the diagnostic and prognostic work-up of CAD. Article see p 678 In daily clinical routine, diagnostic myocardial perfusion is most frequently estimated by single-photon emission CT (SPECT) using 99Tc-labeled radiopharmaceuticals, whereby the tracer uptake in the left ventricular myocardium is analyzed semiquantitatively. Compared with SPECT, PET presents advantages with respect to spatial and temporal resolution, leading to higher sensitivity for the detection of perfusion defects.10 Furthermore, PET perfusion tracers, such as 13N-ammonia or 15O-water, have a higher extraction from the blood …