OBJECTIVE: To summarize the novel evidence for maintaining normoglycemia with intensive insulin therapy during intensive care in critically ill patients, with or without diabetes, in the surgical intensive-care unit. RESULTS: Although the association between hyperglycemia and adverse outcomes of trauma or surgical procedures necessitating intensive care was known, only one intervention study has investigated the causality of this association. This study showed that tight blood glucose control with insulin, aiming for strict normoglycemia (80 to 110 mg/dL or 4.5 to 6.1 mmol/L) during intensive care, dramatically decreased morbidity and mortality. The clinical benefits were present whether or not patients had previously diagnosed diabetes, and they seemed independent of severity and type of critical illness. Multivariate logistic regression analysis indicated that metabolic control, rather than insulin dose per se, statistically explains the beneficial effects of intensive insulin therapy on outcomes of critical illness. Other metabolic effects besides blood glucose control, however, such as normalization of dyslipidemia, and immunologic effects, such as suppression of excessive inflammation and improvement of macrophage function, accompany glycemic control in critically ill patients. These effects seem to surpass the level of glycemic control in explaining the clinical benefits of intensive insulin therapy on sepsis, organ failure, and death. Ongoing studies are attempting to clarify the mechanisms that underlie the beneficial effects of this simple and cost-saving intervention. CONCLUSION: The available evidence favors targeting normoglycemia (blood glucose levels of less than 110 mg/dL or 6.1 mmol/L) by insulin infusion in all adult surgical intensive-care patients. Whether these findings are applicable to nonsurgical intensive-care or to pediatric patients in the intensive care unit remains unclear.