Spinal cord injury (SCI) with resultant quadriplegia or high paraplegia is associated with significant dysfunction of the sympathetic nervous system. This alteration of sympathetic nervous system activity occurs as a consequence of loss of supraspinal control of the sympathetic nervous system and is further complicated by at least three subsequent phenomena that occur below the level of SCI: reduced overall sympathetic activity, morphologic changes in sympathetic preganglionic neurons, and peripheral alpha-adrenoceptor hyperresponsiveness. Reduced sympathetic activity below the level of SCI appears to result in orthostatic hypotension, low resting blood pressure, loss of diurnal fluctuation of blood pressure, reflex bradycardia, and, rarely, cardiac arrest. Peripheral alpha-adrenoceptor hyperresponsiveness likely accounts for some, if not the majority, of the excessive pressor response in autonomic dysreflexia and may also contribute to decreased blood flow in the peripheral microcirculation, potentially increasing susceptibility to pressure sores. What has yet to be established is whether this alpha-adrenoceptor hyperresponsiveness is a consequence of receptor hypersensitivity or a failure of presynaptic reuptake of noradrenaline at the receptor level. Better understanding of the pathophysiology of sympathetic nervous system dysfunction after high-level SCI should allow development of more effective measures to manage clinical complications.