Traumatic brain injury (TBI) is a common cause of neurological morbidity globally, and neurologic sequelae may occur even in the setting of mild injury. At present, the tools that guide diagnostic and prognostic evaluation of patients who suffer from TBI remain limited, especially for prehospital evaluation. Biomarkers of brain injury hold promise in facilitating early management and triage decisions in the civilian and military settings. The identification of biomarkers of brain injury may also be helpful in guiding end-of-life decision making and may facilitate the design of neuroprotective trials.