Much attention has been paid recently to the possibility that oscillating glucose may superimpose on glycated haemoglobin (HbA(1c)) in determining the risk for diabetes complications. Furthermore, recent evidence suggests that glucose variability, particularly if accompanied by frequent hypoglycaemic episodes, may adversely alter the prognosis of acutely ill patients. In vitro and animal studies confirm that oscillating glucose is more dangerous than stable constant high glucose, particularly in activating the pathways involved in the pathogenesis of diabetes complications. The production of free radicals, accompanied by an insufficient increase in intracellular antioxidant defences, seems to account for this phenomenon. In humans, studies also confirm that fluctuating glucose levels produce an increase in free radicals as well as endothelial dysfunction, and that these changes are greater than those produced by stable high glucose. Avoiding glucose fluctuations in diabetic patients and in critically ill patients seems to be an emerging therapeutic challenge.