Acute spinal cord injury (ASCI) occurs as a result of physical disruption of spinal cord axons through the epicenter of injury leading to deficits in motor, sensory, and autonomic function. This is a debilitating neurological disorder common in young adults that often requires life-long therapy and rehabilitative care, placing a significant burden on our healthcare system. While no cure exists, research has identified various pharmacological compounds that specifically antagonize primary and secondary mechanisms contributing to the etiology of ASCI. Several compounds including methylprednisolone (MPSS), GM-1 ganglio-side, thyrotropin releasing hormone (TRH), nimodipine, and gacyclidine have been tested in prospective randomized clinical trials of ASCI. MPSS and GM-1 ganglioside have shown evidence of modest benefits. Clearly trials of improved neuroprotective agents are required. Promising potential therapies for ASCI include riluzole, minocycline, erythropoietin, and the fusogen polyethylene glycol, as well as mild hypothermia.