In recent years glycaemic variability (GV) has emerged as a determinant of vascular complications of both type 1 and type 2 diabetes mellitus. In type 1 diabetes analysis of data of GV show conflicting results on both micro- and macro-vascular complications. In non-diabetic subjects blood glucose after loading is a stronger predictor of cardiovascular complications than fasting glucose. In type 2 diabetes both coefficient of variation of fasting blood glucose and postprandial blood glucose predict cardiovascular events. Also, long term variability of HbA1c has been associated predominantly with diabetic nephropathy, less frequently with retinopathy. Intervention trials to evaluate the effect of postprandial glucose have been conducted only in prediabetes or in type 2 diabetes and the data are not conclusive. In vitro and in vivo data have shown the mechanisms that are at the basis of the adverse cardiovascular effects of GV, mainly associated with oxidative stress; the atherogenic action of postprandial glucose also involves insulin sensitivity, postprandial increase in serum lipids and glycaemic index of food. Thus, correction of GV emerges as a target to be pursued in clinical practice in order to safely reduce mean blood glucose (and thus glycated haemoglobin) and for its direct effects on vascular complications of diabetes.