The National Institute of Child Health and Human Development (NICHD) held a workshop on hypothermia as a potential treatment modality for perinatal hypoxic-ischemic encephalopathy (HIE) in May 2005. A panel of experts summarized the current evidence on the efficacy and safety of hypothermia and reviewed knowledge gaps. The panel concluded that mild, therapeutic hypothermia offered a potential for short-term benefits (up to 18 months of age) when used under strict experimental protocols in term infants. However, these findings have not been tested in preterm infants or severely growth-restricted infants with asphyxia. Many questions still remained about the optimal use of hypothermia for HIE in term infants, including the incidence of possible rare, short-, and long-term side effects. Moreover, the longer-term benefits in neurodevelopmental outcomes after hypothermia for HIE remain to be shown. Because of these and other reasons, the panel concluded that at the current time, therapeutic hypothermia for perinatal HIE should be considered an evolving therapy, the longer-term safety and efficacy of which are still to be established. The panel offered a framework for patient care emphasizing the need for standardized protocols for treatment and follow-up, including school-age outcome assessments. Research priorities were also recommended. The panel strongly urged that the ongoing hypothermia trials should be continued to enable assessment of its efficacy and safety. It recommended the formation of national and international HIE registries, so that scientific progress in this field can be assessed continuously to develop, refine, and optimize therapies for HIE.