For more than 100 yr, scientists have studied the sympathetic nervous system and its cardiovascular control mechanisms. Muscle sympathetic activity is the most important direct and rapidly responding variable for evaluation of sympathetic neural outflow. Because of its significance in response to environmental challenges and its role in cardiovascular control, great attention has been paid to the sympathetic nervous system in both health and disease and, more recently, also during general anesthesia. In fact, general anesthesia can also be considered as an investigational tool to assess mechanisms of cardiovascular regulation. This review evaluates different methods for determination of sympathetic nervous system activity and describes its role in human neurohumoral circulatory control. Furthermore, the effects of general anesthesia on sympathetic nervous system activity and their relevance for clinical anesthesia are discussed.