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BACKGROUND CONTEXT: The past three decades have witnessed increasing interest in strategies to improve neurologic function after spinal cord injury. As progress is made in our understanding of the pathophysiologic events that occur after acute spinal cord injury, neuroprotective agents are being developed. PURPOSE: Clinicians who treat acute spinal cord injuries should have a basic understanding of the pathophysiologic processes that are initiated after the spinal cord has been injured. A familiarity with the literature on which the current use of methylprednisolone is based is also essential. STUDY DESIGN/SETTING: Literature review. METHODS: Literature review of animal data on pathophysiologic mechanisms, and of both animal and human trials of neuroprotective agents. RESULTS: The mechanical forces imparted to the spinal cord cause primary damage to the neural tissue, but a complex cascade of …