The sympathetic nervous system has profound influences on myocardial function and pathophysiology. The heart is densely innervated with sympathetic nerves, which are distributed on a regional basis. Heterogeneity of myocardial sympathetic innervation, or autonomic imbalance, has long been hypothesized as a major mechanism underlying sudden cardiac death. Only in the past few years has it been possible to evaluate abnormalities in heart innervation in the intact animal. Recent developments in cardiac imaging have lead to the ability to map the distribution of the sympathetic nerves in vivo, with radiolabeled metaiodobenzylguanidine. As a result, pathophysiologic mechanisms that relate alterations in sympathetic nerve activity to disease processes are now being explored.