One of the big challenges in neuroscience that remains to be understood is why the central nervous system is not able to regenerate to the extent that the peripheral nervous system does. This is especially problematic after traumatic injuries, like spinal cord injury (SCI), since the lack of regeneration leads to lifelong deficits and paralysis. Treatment of SCI has improved during the last several decades due to standardized protocols for emergency medical response teams and improved medical, surgical, and rehabilitative treatments. However, SCI continues to result in profound impairments for the individual. There are many processes that lead to the pathophysiology of SCI, such as ischemia, vascular disruption, neuroinflammation, oxidative stress, excitotoxicity, demyelination, and cell death. Current treatments include surgical decompression, hemodynamic control, and methylprednisolone. However, these early treatments are associated with modest functional recovery. Some treatments currently being investigated for use in SCI target neuroprotective (riluzole, minocycline, G-CSF, FGF-2, and polyethylene glycol) or neuroregenerative (chondroitinase ABC, self-assembling peptides, and rho inhibition) strategies, while many cell therapies (embryonic stem cells, neural stem cells, induced pluripotent stem cells, mesenchymal stromal cells, Schwann cells, olfactory ensheathing cells, and macrophages) have also shown promise. However, since SCI has multiple factors that determine the progress of the injury, a combinatorial therapeutic approach will most likely be required for the most effective treatment of SCI.