Purpose of Review The present article reviews the pathophysiology of cardiac sympathetic denervation, the principles of positron emission tomography (PET) imaging of the sympathetic innervation of... Show morePurpose of Review The present article reviews the pathophysiology of cardiac sympathetic denervation, the principles of positron emission tomography (PET) imaging of the sympathetic innervation of the heart and its potential clinical role, based on current and expected future evidence. Recent Findings Imaging of cardiac sympathetic denervation can be performed with radiolabeled noradrenaline analogues, e.g., C-11-hydroxyephedrine. A greater burden of sympathetic denervation carries prognostic significance, e.g., in patients with ischemic cardiomyopathy and a left ventricular ejection fraction <= 35%, who are more likely to experience sudden cardiac death. Abnormalities of sympathetic cardiac innervation have been demonstrated in hypertrophic, dilated, and arrhythmic right ventricular cardiomyopathies, and may be helpful in better phenotyping patients who will benefit from device therapy, e.g., cardiac resynchronization and implantable cardioverter-defibrillator implantation. The results of future trials, e.g., the Prediction of Arrhythmic Events with Positron Emission Tomography (PAREPET) II study, are awaited to inform on the role of PET cardiac sympathetic imaging in the selection of device therapy. PET cardiac sympathetic innervation imaging allows visualization and quantification of autonomic denervation secondary to various cardiac diseases, and has significant potential to influence clinical decision-making, e.g., the titration of pharmacotherapy and more directed selection of candidates for device implantation. Show less