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This article reviews published experimental and clinical evidence for the benefits of modest hypothermia in the treatment of traumatic brain injury (TBI). Therapeutic hypothermia has been reported to improve outcome in several animal models of CNS injury and has been successfully translated to specific patient populations. A PubMed search for hypothermia and TBI was conducted, and important papers were selected for review. The research summarized was conducted at major academic institutions throughout the world. Experimental studies have emphasized that hypothermia can affect multiple pathophysiological mechanisms thought to participate in the detrimental consequences of TBI. Published data from several relevant clinical trials on the use of hypothermia in severely injured TBI patients are also reviewed. The consequences of mild to moderate levels of hypothermia introduced by different strategies to the head-injured patient for variable periods of time are discussed. Both experimental and clinical data support the beneficial effects of modest hypothermia following TBI in specific patient populations. Following on such single-institution studies, positive findings from multicenter TBI trials will be required before this experimental treatment can be considered standard of care.