OBJECTIVE: To review the components of glycemic control in patients with diabetes and discuss the factors contributing to development of complications. METHODS: The findings in various published reports are summarized, particularly in reference to metabolic alterations, treatment, and long-term outcomes in diabetes. RESULTS: Hemoglobin A1c, an integrated marker of overall glucose exposure, is the standard for monitoring glycemic control. The results in the United Kingdom Prospective Diabetes Study indicated that each 1% decrease in hemoglobin A1c reduced the risk for mortality associated with diabetes by 21% and the risk for myocardial infarction by 14%. Nevertheless, fasting plasma glucose and postprandial glucose levels are well-defined targets for therapy. Numerous epidemiologic studies also support the concept that excessive glucose excursion after ingestion of an oral glucose load is associated with an independent risk for cardiovascular disease that is greater than the one associated with the fasting plasma glucose level. Hyperglycemia apparently activates different metabolic pathways that may contribute to development of microangiopathy and macroangiopathy. Intensive treatment to maintain strict glycemic control has been shown to yield better control of diabetes-related complications in comparison with conventional therapy. CONCLUSION: The complexity of the metabolic alterations in diabetes must be fully recognized, and a comprehensive approach to management should be considered.