Clinically significant neuroprotection for the brain continues to be an elusive quest. All attempts at developing effective pharmacologic agents have failed in clinical trials. Hypothermia has been thought to confer protection after brain injury for many years, but has recently regained interest as a neuroprotectant for focal ischemic stroke in the basic science and clinical literature. The failure to develop safe and efficacious pharmacologic agents along with promising clinical data on the efficacy of hypothermia for cardiac arrest patients have raised a great interest in hypothermia as a neuroprotectant for ischemic stroke. As a clinically meaningful neuroprotectant for stroke, hypothermia confers several theoretical advantages over pharmacologic agents. A major problem with neuroprotectant therapy is instituting therapy within a narrow time window. This obstacle may be easier for hypothermia to overcome as emergency medical service personnel can theoretically initiate it in the field. Additionally, pharmacologic agents are usually restricted to one aspect of the pathophysiologic cascade triggered by focal ischemia, whereas hypothermia acts on several of these pathways simultaneously. The recent advances and future directions in the utilization of hypothermia as a potential therapy for focal ischemic stroke are reviewed.