This chapter reviews the etiology of brain injury in surgical patients receiving general anesthesia. Traumatic brain injury, cardiac arrest, perinatal asphyxia and acute stroke are common conditions that have published evidence-based guidelines on neuroresuscitation that are beyond the scope of the review. Cerebral ischemia is one of the leading causes of brain injury. Prevention of acute brain injury in the clinical setting is primarily based on two tenets, delivery of substrate and reduction of cerebral metabolic rate of oxygen2 and cerebral metabolic rate for glucose. Clinical trials of hyperoxia in brain injured patients have not demonstrated any clinical benefit. Hypothermia has shown clear benefit against brain injury in the laboratory. Hypothermia reduces cellular metabolic rates and oxygen consumption linearly and is an effective way to protect organ function. The neuroprotective effect of prophylactic hypothermia was tested in a randomized control trial comparing mild hypothermia to normothermia in patients undergoing aneurysm surgery.