Hyperglycemia is frequent during critical illness and is perceived by the clinician as part of the systemic metabolic response to stress. Of all patients with "stress hyperglycemia" only one third are known to have diabetes mellitus. Previous studies reported that patients presenting hyperglycemia during acute illness have an increased risk for nosocomial infections. Morbidity and mortality also increases in patients with myocardial infarction or stroke who develop hyperglycemia. Contemporary medical practice states that hyperglycemia under these conditions should only be treated with insulin if blood glucose levels are > 200 mg/dl. A recent trial showed that intensive insulin treatment of critically ill patients in the intensive care unit with the goal of maintaining blood glucose levels between 80 and 110 mg/dl significantly reduced morbidity and mortality without significant risk of hypoglycemia. These benefits of insulin treatment are not yet well understood, but some pathophysiological evidence suggests that hyperglycemia contributes to perpetuate the systemic proinflammatory response, and insulin--a natural endogenous hormone that has a major role in the intermediary metabolism--participates actively in the systemic anti-inflammatory response. As a result of these findings, we recommend that hyperglycemia during critical illness should be treated with insulin, in order to achieve blood glucose levels in a normal range, regardless of whether or not these patients have diabetes mellitus.