Pathophysiological stress from acute illness causes metabolic disturbance, including altered hepatic glucose metabolism, increased peripheral insulin resistance and hyperglycaemia. Acute hyperglycaemia is associated with increased morbidity and mortality in patients in intensive care units and patients with acute respiratory disease. The present review will consider mechanisms underlying this association. In normal lungs the glucose concentration of airway secretions is approximately 10-fold lower than that of plasma. Low airway glucose concentrations are maintained against a concentration gradient by active glucose transport. Airway glucose concentrations become elevated if normal homeostasis is disrupted by a rise in blood glucose concentrations or inflammation of the airway epithelium. Elevated airway glucose concentrations are associated with and precede increased isolation of respiratory pathogens, particularly methicillin-resistant Staphylococcus aureus, from bronchial aspirates of patients intubated on intensive care. Markers of elevated airway glucose are associated with similar patterns of respiratory infection in patients admitted with acute exacerbations of chronic obstructive pulmonary disease. Glucose at airway concentrations stimulates the growth of respiratory pathogens, over and above the effect of other nutrients. Elevated airway glucose concentrations may also worsen respiratory disease by promoting local inflammation. Hyperglycaemia may thus promote pulmonary infection, at least in part, by an effect on airway glucose concentrations. Therapeutic options, including systemic control of blood glucose and local manipulation of airway glucose homeostasis, will be considered.