Background: Hyperglycemia is a common occurrence in critically ill patients. Recent evidence has demonstrated improved survival in patients in surgical intensive care units (SICUs) receiving "tight glycemic control." The mechanisms of this survival advantage are not well understood. Methods: A review of the English language literature pertaining to potential mechanisms affecting outcome in critically ill patients receiving insulin therapy, including recently published human trials evaluating mortality outcomes. Results: This review discusses the results of clinical trials of "tight glycemic control," considers mechanisms of hyperglycemia in critical illness, and reviews potential mechanisms of improved outcome related in the critically ill patient. Conclusions: A number of human studies have demonstrated improved outcomes in critically ill patient populations receiving insulin therapy with a target of euglycemia, suggesting at least part of the benefit of this therapy is normal blood sugar and not the effects of insulin. An important population not studied to date is patients in the medical ICU. However, aggressive control of hyperglycemia now remains an important component of care for all surgical patients in the ICU.