Acute injury to the spinal cord initiates a sequence of vascular, biochemical, and inflammatory events that result in the development of secondary tissue damage. Experimental studies and clinical trials in humans have demonstrated that the extent of this secondary tissue damage can be limited by pharmacologic intervention at appropriate intervals after injury. High doses of methylprednisolone sodium succinate (MPSS) improve the outcome of acute spinal cord injury in humans if treatment is initiated within 8 hours of injury. Starting therapy more than 8 hours after injury is detrimental to outcome. The clinical efficacy of methylprednisolone in improving the outcome of canine spinal cord injuries has not yet been demonstrated and its use by veterinarians is controversial. Many dogs are not seen by a veterinarian within the 8-hour window after injury, and these dogs frequently are treated with nonsteroidal anti-inflammatory drugs or large doses of dexamethasone or prednisone before methylprednisolone treatment can be initiated, thus increasing the risk of severe adverse effects. Other drugs that may provide safer and more effective alternatives to methylprednisolone include thyrotropin-releasing hormone (TRH), the 21-aminosteroids, and kappa opioid agonists. Recent studies suggest that modulation of the influx of inflammatory cells and activation of endogenous microglial cells may provide another means of improving the outcome of acute spinal cord injuries. Many drugs being developed to treat acute spinal cord injury have shown promising results when evaluated experimentally. However, any proposed therapeutic strategy should be evaluated in prospective blinded clinical trials before being adopted in clinics.