OBJECTIVE Hyperglycemia is common during perioperative management of surgical and critically ill patients. There is extensive ongoing study of detrimental effects associated with hyperglycemia, with several remaining unanswered questions. This review discusses recent literature on tight glucose control with insulin therapy and its effects in prevention and management of infection. RESULTS Hyperglycemia affects multiple pathways of the immune system, resulting in decreased phagocytic and chemotactic functions in neutrophils and monocytes, as well as increased rates of apoptosis of the former and decreased ability of the latter to present antigen. Intensive insulin therapy has been shown to counteract many of these deleterious effects. Clinically, the benefits of tight glucose control have been evaluated in different patient populations with conclusions that remain varied. Hypoglycemia as a complication of tight glucose control continues to be an issue and has led to discontinuation of two large-scale studies. The clinical relevance of hypoglycemic events remains unclear. CONCLUSIONS Hyperglycemia impairs the cellular immune system, stimulates inflammatory cytokines, and affects the microcirculation, thus increasing risk for infection and preventing normal wound healing. Additional investigation is needed to define appropriate patient populations and to develop effective treatment strategies for preventing perioperative morbidity.