OBJECTIVES Large prospective clinical studies in both type 1 Diabetes Mellitus (T1DM) and type-2 diabetes mellitus (T2DM) have shown that high HbA1c levels is a strong predictor of diabetic complications. New data suggest that variability in glucose values, specifically excursions in postprandial hyperglycemia, may also play a significant role in the risk of microvascular and macrovascular complications. The aim of this review was to assess the published evidence for an association between glycemic variability and diabetic complications in patients with DM. METHODS A systematic review of studies published in English between 1990-November 2008 was undertaken. Studies in patients with T1DM or T2DM reporting a) measures of glycemic variability; and b) its impact on the development or progression of diabetic complications were assessed. RESULTS Eighteen studies were identified. Seven and 11 studies focused on T1DM and T2DM patients, respectively. Studies in patients with T1DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two T1DM studies did glucose variability have a significant association with prevalent peripheral neuropathy and presence of nephropathy, but not with other complications. Among T2DM studies, a significant positive association between glucose variability and the development or progression of diabetic complications was reported in 10 of 11 studies. The risk of progression to diabetic retinopathy was significantly increased among patients in higher quartiles of glycemic variability (CV-FPG): 2nd quartile OR=3.47 (95%CI:1.06-11.5); 3rd quartile OR=3.66 (95%CI:1.12-12); and 4th quartile OR=6.95 ((95%CI:2.1-22.4). Similarly, the risk of all cause and cardiovascular mortality was significantly higher among patients in the 2nd and 3rd tertiles of CV-FPG. CONCLUSIONS This overview of the available evidence suggests that glucose variability may be an independent predictor of complications regardless of HbA1c levels in patients with T2DM. Better control of blood glucose excursions may reduce the risk of these complications.