It has been known since the earliest direct recordings that postganglionic sympathetic nerve activity shows a respiratory modulation in humans. Sympathetic outflow to the skeletal muscle vasculature reaches a nadir at peak inspiration and peaks during expiration. This pattern of activity is the net result of a complex integration of central neuronal circuits and modulatory feedback signals from cardiorespiratory sensory afferents, including lung-stretch receptors, baroreceptors, central and peripheral chemoreceptors. There is accumulating evidence from animal models and patient populations indicating that pathophysiological alterations in the respiratory modulation of sympathetic nerve activity can occur. Simms et al. (2009) reported that an altered coupling between respiration and sympathetic nerve activity is a causative factor in the elevated vascular resistance and blood pressure observed in the spontaneously hypertensive rat. We have observed an attenuation of the normal cyclical inhibition of muscle sympathetic nerve activity burst incidence during respiration in our preliminary studies of patients with essential hypertension (Fisher et al. 2011). Similar findings have been reported in patients with chronic heart failure, where a diminished sympathoinhibitory effect of the lung inflation reflex has been closely related to heightened muscle sympathetic nerve activity (Goso et al. 2001). Interestingly, acute slow deep breathing transiently reduces muscle sympathetic nerve activity in patients with hypertension (Oneda et al. 2010). Ongoing studies in our laboratory are examining the effects of a home-based training device which guides slow deep breathing (8 weeks, 15 min daily) on resting sympathetic nerve activity and its respiratory modulation in patients with hypertension.