In this article, the role of modest hypothermia for the treatment of experimental and clinical spinal cord injury (SCI) is discussed. While early investigations evaluated the beneficial effects of more profound levels of local hypothermia treatment following SCI, recent studies have concentrated on the benefits of mild hypothermia in protecting and promoting functional recovery in established animal models. In this regard, using preclinical models of both thoracic and cervical contusive SCI, early cooling strategies using systemically administered mild hypothermia (33°C) have been reported to improve locomotive function as well as forelimb gripping strength and coordination. Recently, the effects of modest hypothermia in severely injured SCI patients have also been tested. Modest systemic hypothermia was reported to be both safe and achievable in severely injured SCI patients. This evidence-based review summarizes both experimental and clinical data to support the use of modest hypothermia in the acute SCI setting.