ABSTRACT: Treatment of acute stroke is difficult due to the complexity of events triggered by ischemic insult. Current reperfusion strategies are time limited and, alone, may not be sufficient to achieve maximal neurologic outcomes. Therapeutic hypothermia (TH) appears to be a promising neuroprotective therapy, as it affects a wide range of destructive mechanisms occurring in ischemic brain tissue. Animal research has substantiated the use of TH in acute stroke. Human studies utilizing TH in acute stroke have shown trends toward positive effects; however, there have been a variety of measurements and methods making comparisons difficult. The ideal protocol for the use of TH in stroke has not yet been developed and requires determination of optimal depth, duration, and methods of temperature measurement and cooling for acute stroke. The purposes of this article were to (1) discuss the effects of ischemia and reperfusion in acute stroke, (2) discuss how TH can potentially limit neurological injury, and (3) review current literature on the use of hypothermia as a treatment for acute stroke.