Therapeutic moderate hypothermia has been advocated for use in traumatic brain injury, stroke, cardiac arrest-induced encephalopathy, neonatal hypoxic-ischemic encephalopathy, hepatic encephalopathy, and spinal cord injury, and as an adjunct to aneurysm surgery. In this review, we address the trials that have been performed for each of these indications, and review the strength of the evidence to support treatment with mild/moderate hypothermia. We review the data to support an optimal target temperature for each indication, as well as the duration of the cooling, and the rate at which cooling is induced and rewarming instituted. Evidence is strongest for prehospital cardiac arrest and neonatal hypoxic-ischemic encephalopathy. For traumatic brain injury, a recent meta-analysis suggests that cooling may increase the likelihood of a good outcome, but does not change mortality rates. For many of the other indications, such as stroke and spinal cord injury, trials are ongoing, but the data are insufficient to recommend routine use of hypothermia at this time.