Traumatic brain injuries (TBIs) are the most common disabling injuries in the United States, accounting for 44% of all deaths due to trauma. Once inflicted, primary cerebral injury is immutable and irreversible. Consequently, initial critical care of TBI patients focuses on prevention of secondary cerebral injury through the treatment of intracranial hypertension, systemic resuscitation, and multisystem stabilization. Relationships exist between therapeutic positioning, multisystemic stability, and prevention of secondary cerebral injury in severe TBI. A critical review and synthesis of current research literature on multisystem responses to positioning led to development of clinical recommendations based on currently available evidence and generated best practices for positioning patients with severe TBI.