Over the past 15 years it has been recognized that the temperature of the brain has an important influence on the extent of brain injury that follows intervals of hypoxia-ischemia. Available data in animals and humans show that brain injury is worsened when fever is superimposed on an ischemic event. Furthermore, data in neonates and adults strongly suggest a neuroprotective role for modest hypothermia (temperature reductions of 1 to 6 degrees C) applied during or following ischemia or hypoxia-ischemia. This article provides an overview of the effects of brain temperature, including its role in the development of brain injury, mechanisms of brain injury which may be temperature sensitive, the regulation of brain temperature, thermal characteristics during brain cooling, and current clinical investigations that use temperature as a therapeutic modality.