The sympathetic division of the nervous system is critical for maintaining both resting arterial pressure and for producing changes in regional perfusion required by behavioral state changes. A primary determinant of arterial pressure is the level of vasoconstriction within skeletal muscle. It is well established that there is a tight relationship between dynamic changes in arterial pressure and muscle sympathetic nerve activity (MSNA) through the workings of the baroreflex. While the central circuitry underlying the baroreflex has been extensively investigated in anesthetized experimental animals, few studies have investigated the central circuitry responsible for the baroreflex in awake human subjects. Recently we were the first to record concurrently MSNA (using microneurography) and brain activity (using functional magnetic resonance imaging) in awake humans in a series of experiments designed to determine the central circuitry underlying the baroreflex in humans. We confirmed that the baroreflex involves activity changes within the nucleus tractus solitarius, caudal ventrolateral, and rostral ventrolateral medulla. Because conditions such as essential hypertension, obesity, and obstructive sleep apnea are all characterized by significant increases in resting MSNA, it is important to understand both brainstem and cortical sites involved in regulating resting levels of MSNA. Future investigations which define cortical sites involved in generating and modulating MSNA are important if we are to understand the underlying mechanisms of many conditions characterized by hypertension. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.