Hyperglycaemic hyperosmolar non-ketotic syndrome (HHNS) is a life-threatening complication of uncontrolled diabetes mellitus. This syndrome is characterised by severe hyperglycaemia, a marked increase in serum osmolality, and clinical evidence of dehydration without significant accumulation of ketoacids. HHNS is typically observed in elderly patients with non-insulin-dependent diabetes mellitus, although it may rarely be a complication in younger patients with insulin-dependent diabetes, or those without diabetes following severe burns, parenteral hyperalimentation, peritoneal dialysis, or haemodialysis. Patients receiving certain drugs including diuretics, corticosteroids, beta-blockers, phenytoin, and diazoxide are at increased risk of developing this syndrome. Patients usually present with a prolonged phase of osmotic diuresis leading to severe depletion of both the intracellular and extracellular fluid volumes. Losses of water exceed those of sodium, resulting in hypertonic dehydration. Therefore, correction of the syndrome will ultimately require administration of hypotonic fluids. Patients presenting with HHNS also have significant depletion of potassium and other electrolytes that will need to be replaced. The principal goal at the outset of therapy must be restoration of the intravascular volume to assure adequate perfusion of vital organs. It remains controversial whether 0.9% or 0.45% NaCl should be the initial fluid infused intravenously. We prefer to administer 0.9% NaCl until the vital signs have stabilised and then substitute 0.45% NaCl. 10 to 15 units of regular human insulin should be injected as a bolus, followed by a continuous infusion of approximately 0.1 U/kg/h. Once the blood glucose approaches 13.9 to 16.7 mmol/L (250 to 300) mg/dl, 5% dextrose should be added to the intravenous fluids and the rate of insulin infusion reduced. Following recovery many patients presenting with HHNS will not require long term insulin therapy and can be managed effectively with diet or oral agents. Precipitating causes of HHNS must be identified and treated simultaneously with correction of the metabolic abnormalities. Appropriate management of precipitating illnesses will limit the high mortality associated with HHNS. This review discusses the current state of knowledge concerning the pathogenesis of HHNS, the clinical features of the disorder, and a systematic approach to treatment.