Cerebral ischemia causes a rapid decline in the ability of brain mitochondria to synthesize adenosine triphosphate when they are exposed to oxygen and oxidizable substrates. Ischemia also results in a decreased capacity for energized mitochondria to sequester the abnormally high levels of calcium that are present within ischemic tissue. The degree to which these processes are affected is likely to influence the maintenance of cell viability during cerebral resuscitation. Factors that have been proposed to account for mitochondrial damage during ischemia and reperfusion include intracellular acidosis, Ca2+-induced membrane damage, and free-radical-dependent membrane lipid peroxidation. Ongoing research indicates that measures can be taken to manipulate these factors so that mitochondrial damage may be minimized and cell viability optimized during resuscitation.