Brain injury rehabilitation prior to the 1980s emphasized the restorative properties of systematic, graded exercise overseen by physical, occupational, and speech-language therapists in inpatient hospital settings. A comprehensive review of pharmacotherapy in traumatic brain injury (TBI) published in 2014 provides a current overview of these concepts and the need for future studies. The neurophysiological basis of rehabilitation represents a learning paradigm not dissimilar in nature to that commonly seen in normal human neurodevelopment and learning. Inefficient or insufficient sleep results in neurocognitive abnormalities, including impaired working memory, impaired phasic attention, and reduced speed of information processing as has been noted in shift workers and medical house staff. Extreme malnourishment, whether generalized or protein in nature, has a recognized impact on the experience-related neuroplasticity of children. Nutritional stability becomes a component of prepharmacologic intervention following neurotrauma. Treatment with inappropriate analgesics or escalating doses of ineffective analgesics and centrally acting muscle relaxants to reduce spasm result in attenuated or disrupted cognitive recovery.