Experimental studies in animal spinal cord injury models suggest that preservation of a relatively small number of spinal axons can support neurological recovery. The second National Acute Spinal Cord Injury Study (NASCIS 2) was the first clinical trial to demonstrate that a treatment given after injury can enhance neurological recovery. In this trial, patients treated with high-dose methylprednisolone within 8 hours of spinal cord injury recovered more sensory and motor function than did those treated with placebo. In addition to demonstrating the first effective pharmacological intervention in central nervous system injury, NASCIS 2 identified several critical issues that must be investigated in future preclinical and clinical research. These include drug dose, initiation time, and duration of treatment, as well as combination therapy and injury severity. Addressing these issues systematically will require more reproducible animal models and more accurate outcome measures.