The autonomic nervous system (ANS), composed of the sympathetic and parasympathetic nervous systems, acts to maintain homeostasis in the body through autonomic influences on the smooth muscle, cardiac muscles, blood vessels, glands and organs of the body. The parasympathetic nervous system interacts via the cranial and sacral segments of the central nervous system, and the sympathetic nervous system arises from the T1–L2 spinal cord segments. After a spinal cord injury (SCI), supraspinal influence on the ANS is disrupted, leading to sympathetic blunting and parasympathetic dominance resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions and uncontrolled bowel, bladder, and sexual dysfunction. Further, afferent signals to the sympathetic cord elicit unabated reflex sympathetic outflow in response to noxious stimuli below the level of SCI. This article outlines the pathophysiology of SCI on the ANS, clinical ramifications of autonomic dysfunction, and the potential long-term sequelae of these influences following SCI.