AbstractThe remarkable advances in survival of infants with congenital heart disease who undergo cardiac surgery are due in large part to techniques that require periods of markedly decreased or arrested circulation. An obvious prerequisite has been the development of techniques that protect critical organ systems, particularly the nervous system, during the often prolonged periods of attenuated oxygen delivery. Despite the manifest success of current neuroprotective strategies, a substantial postoperative neurologic morbidity persists in these infants. The planned periods of hypoperfusion provide a unique clinical opportunity for the prospective, in vivo study of cerebral responses to hypoxic‐ischemic stress. Furthermore, the potential for pretreatment intervention is likely to make this an active setting for the clinical trial of future neuroprotective strategies. This article will evaluate the strengths and limitations of this clinical model, with particular reference to the mechanisms of hypoxia‐ischemia and potential interventions. MRDD Research Reviews 3:49–58, 1997. © 1997 Wiley‐L