This article reviews the pathophysiology of spinal cord injury. The focus is on the role of post-traumatic membrane lipid changes, including lipid hydrolysis with enzymatic lipid peroxidation (ie, eicosanoid production) and nonenzymatic, free radical-induced lipid peroxidation in the secondary autodestruction of injured spinal cord tissue. A speculative etiopathogenesis of secondary injury is presented in an attempt to explain the importance and order of the pathophysiologic events that result in tissue death and the apparent effectiveness of diverse pharmacologic agents in the treatment of experimental spinal cord injury.