The field of nuclear cardiology is witnessing growing interest in the use of cardiac PET for the evaluation of patients with coronary artery disease (CAD). The available evidence suggests that myocardial perfusion PET provides an accurate means for diagnosing obstructive CAD, which appears superior to SPECT especially in the obese and in those undergoing pharmacologic stress. The ability to record changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion (in mL/min/g of tissue) provides an added advantage over SPECT for evaluating multivessel CAD. There is growing and consistent evidence that gated myocardial perfusion PET also provides clinically useful risk stratification. Although the introduction of hybrid PET/CT technology offers the exciting possibility of assessing the extent of anatomic CAD (CT coronary angiography) and its functional consequences (ischemic burden) in the same setting, there are technical challenges in the implementation of CT-based transmission imaging for attenuation correction. Nonetheless, this integrated platform for assessing anatomy and biology offers a great potential for translating advances in molecularly targeted imaging into humans. PET has contributed significantly to advance our understanding of heart physiology and pathophysiology for .25 y. Initially, it emerged as a powerful investigative tool that allowed in vivo quantification of physiologic processes, including myocardial perfusion and metabolism, neuronal and receptor function, and, more recently, molecularly targeted oncologic imaging. Despite its success in research applications, the limited availability of this technology, its increased cost, and the limited data supporting its use and reimbursement have all contributed to the relatively limited clinical acceptance of this imaging technology. Fortunately, there are now clear signs that change is under way. Indeed, the exponential growth in the number of PET/CT systemsattributable primarily to the technology's widely accepted role in clinical oncology-along with the Food and Drug Administration's approval of PET radiopharmaceuticals for cardiac imaging, changes in reimbursement, and the increasing documentation of PET's clinical efficacy have all contributed to help advance its clinical role in cardiovascular medicine.The emergence of integrated PET/CT technology as the dominant configuration of clinical scanners also holds great promise for cardiac imaging as it provides a potential opportunity to delineate the anatomic extent and physiologic severity of coronary atherosclerosis in a single setting. However, the recent rapid growth of PET/CT is now opening a considerable gap between the most sophisticated users of the technology and those with a more limited knowledge base and fewer training opportunities; this includes cardiologists, as well as nuclear medicine specialists, and radiologists, who frequently lack clinical experience in performing and interpreting these cardiovascular procedures. The objective of this review ...