Abstract: Many concepts about acute and chronic effects of stress depend on alterations in sympathetic nerves supplying the heart. Physiologic, pharmacologic, and neurochemical approaches have been used to evaluate cardiac sympathetic function. This article describes a fourth approach that is based on nuclear scanning to visualize cardiac sympathetic innervation and function and relationships between the neuroimaging findings and those from other approaches. Multiple-system atrophy with orthostatic hypotension (formerly the Shy-Drager syndrome) features normal cardiac sympathetic innervation and normal entry of norepinephrine into the coronary sinus (cardiac norepinephrine spillover), in contrast to Parkinson disease with orthostatic hypotension, which features neuroimaging and neurochemical evidence for loss of cardiac sympathetic nerves. This difference may have important implications not only for diagnosis but also for understanding the etiology of Parkinson disease. By analysis of curves relating myocardial radioactivity with time (time-activity curves) after injection of a sympathoneural imaging agent, it is possible to obtain information about cardiac sympathetic function. Abnormal time-activity curves are seen in common disorders such as heart failure and diabetic neuropathy and provide an independent, adverse prognostic index. Analogous abnormalities might help explain increased cardiovascular risk in psychiatric disorders such as melancholic depression.