Ischemic stroke is a leading cause of death and long-term disability, and hyperglycemia is believed to aggravate cerebral ischemia. To review animal and human studies on the relationship between hyperglycemia and brain ischemia that elucidate some of the mechanisms for the deleterious effect of hyperglycemia. To discuss present and future clinical recommendations for glucose control. Computerized data sources and published indexes and articles from 1976 through 2000 were searched for human studies that evaluated the association between stroke and hyperglycemia, and studies focused on experimental models of hyperglycemic animals with focal and global brain ischemia. Most human studies have shown that in acute stroke, admission hyperglycemia in patients with or without diabetes is associated with a worse clinical outcome than in patients without hyperglycemia. This association is more consistent in the nonlacunar type of stroke. Animal studies support these findings by showing both in global and in focal postischemic models that hyperglycemia exaggerates the following damaging processes: intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, blood-brain barrier disruption, and tendency for hemorrhagic transformation. Insulin treatment of hyperglycemic animals was found to have a beneficial effect in focal and global brain ischemia, which may be mediated by the glucose-reduction effect or by a direct neuroprotection. Most studies show the deleterious effect of early hyperglycemia, especially in patients with nonlacunar focal or global ischemia. Clinical trials of intensive insulin treatment are needed. Meanwhile simple measures to avoid excessive hyperglycemia are recommended.