SCI commonly results in permanent loss of partial or full sensation and movement below the level of injury and can therefore be physically and emotionally devastating for patients and their caregivers. The estimated incidence of SCI in Canada is about 4,000 each year (41 per million) (Noonan et al. 2012), with young men being the most common demographic experiencing these accidents (Kirshblum et al. 2002). However, more recently, the Canadian demographic has reported a shift to older adults as a result of falls in the elderly overtaking motor vehicle accidents as the most common cause of injury (Pickett et al. 2006). Regions in Russia, Sweden and Norway also reflect the increasing contribution of falls as the most common etiology of injury (Singh et al. 2014). Although many individuals may never fully recover sensation and movement, patient outcomes have drastically improved with advances in pre-hospital care, emergency care, acute trauma care, surgical interventions, and rehabilitation. Common treatments that have contributed to the decrease in mortality and increase in acute recovery include treating neurogenic shock, hemodynamic resuscitation, spine stabilization, surgery, prophylactics, and pharmaceuticals for neuroprotection to minimize injury. The use of pharmaceuticals for neuroprotection has been the subject of excitement and debate since the 1970s and continues to gain research interest over time. In this chapter, only the evidence that exists for pharmaceutical agents used during the acute phase of SCI will be reviewed; other research avenues of neuroprotection such as stem cell transplants (Kan et al. 2010) and macrophage therapy (Kigerl & Popovich 2006) will be omitted.