Despite increasing understanding of the cellular and molecular mechanisms that cause pathology in children who suffer traumatic brain injury, few advances have been made in developing new effective therapies for such injury. In the past, clinicians treated some neurologically injured patients with the sustained application of systemic hypothermia. This practice was largely abandoned when patients experienced complications; however, interest has been renewed in treatment with milder forms of hypothermia. This review focuses on the clinical and laboratory evidence concerning this therapy. Promising results from two clinical trials are presented. Moreover, evidence is discussed in support of the notion that some children with traumatic brain injury, more so than adults, may benefit from hypothermic therapy. Lastly, putative mechanisms for the effects of hypothermia, including attenuation of injury caused by inflammation, excitotoxic amino acids, nitric oxide, and free radicals, are discussed.