Positron emission tomography (PET) is currently the most sophisticated scintigraphic imaging technique developed for in-vivo quantification of cardiac physiology and biochemistry. The state-of-the-art PET technology allows delineation of regional tracer activity with high spatial and temporal resolution. A large number of radiopharmaceuticals have been developed to study myocardial perfusion enabling accurate diagnosis and localization of coronary artery disease (CAD) and energy metabolism. More recently, newer tracers such as radiolabeled catecholamine analogues allow the pre- and postsynaptic evaluation of cardiac autonomic innervation. Metabolic imaging with PET represents currently the gold standard for tissue viability assessment with well-validated diagnostic and prognostic information. F-18 deoxyglucose has been also used in combination with SPECT or coincidence imaging providing comparable clinical information but without need for the expensive and rarely available imaging technology of PET. The assessment of coronary flow reserve is the most sensitive scintigraphic method to i) detect vascular abnormalities before their hemodynamic significance, ii) diagnose and define the extent of CAD, and iii) to monitor the effects of (non)pharmacological intervention on regional and global cardiac flow. C-11 hydroxyephedrine (HED) allows imaging of sympathetic neuronal function. the course of cardiac reinnervation after cardiac transplantation was demonstrated with C-11 HED PET, and preliminary evidence suggests that this technique might provide prognostic information on sympathetic neuronal status in congestive heart failure, too. The functional and prognostic relevance of PET imaging together with the increased availability of lower cost instrumentation imaging will define its future role in the diagnosis, assessment of extent, prognosis and in the therapeutic decision making of cardiac disease.