The injury spectrum in traumatic brain injury (TBI) encompasses not only the initial insult, but includes the cascade of systemic responses and pathophysiology that occur after the focal or diffuse brain injury. This chapter presents a case study of a 49-year-old male motorcyclist who was evaluated in the emergency room after a motor vehicle collision with an articulated truck. Around the time of computed tomography (CT) scanning, the patient's right pupil became dilated and unreactive. Hypoxic cerebral damage, a common postmortem finding in TBI, is associated with arterial hypoxemia, decreased mean arterial pressure, or cerebral hypoperfusion, occurring as a consequence of shock, intracranial hypertension, or cerebral vasospasm. Although a definitively effective neuroprotective therapy in central nervous system (CNS) trauma remains elusive, through the skilled interactions of prehospital, emergency department, anesthesiology, and surgical personnel, the lives of many critically injured individuals can be saved and their neurologic function preserved.