Spinal cord injury (SCI) pain has a mixture of nociceptive and neuropathic etiologies. There are few controlled studies to guide medical therapy specifically for SCI pain, and so an extrapolation must be made from other painful conditions. This article attempts to establish a rational basis for the trial of pharmacologic agents as treatments for SCI pain. Pain localized to sites above the level of SCI should be approached and treated in an identical fashion to pain in patients without SCIs, with the recognition that some processes are common in SCI populations. Pain localized at or below the level of SCI is more complex, and treatment is more empiric with the use of nociceptive pain medications (anti-inflammatories and opioids) and neuropathic pain medications (e.g., antidepressants, anticonvulsants) directed by features suggestive of those types of pain. Relevant literature related to the treatment of nociceptive and neuropathic pains, in general, and SCI pain, in particular, is reviewed.