OBJECTIVE To review the features of nocturnal hypoglycemia and various preventive strategies. METHODS We discuss the physiologic changes, the potential precipitating factors, the immediate and long-term effects, and the currently available options for treatment of nocturnal hypoglycemia in patients with diabetes. RESULTS Nocturnal hypoglycemia is common in patients with type 1 diabetes and is usually asymptomatic. Nocturnal hyperinsulinemia frequently occurs with insulin therapy, and although blood glucose levels are often low during sleep, they are seldom measured routinely. Almost 50% of all episodes of severe hypoglycemia occur at night during sleep. Such episodes can cause convulsions and coma and have been implicated as a precipitating factor in cardiac arrhythmias resulting in sudden death--the "dead-in-bed syndrome." Nocturnal hypoglycemia seems to have no immediate detrimental effect on cognitive function; however, on the following day, mood and well-being may be adversely affected. Recurrent exposure to nocturnal hypoglycemia may impair cognitive function; other substantial long-term morbidity includes the development of acquired hypoglycemia syndromes, such as impaired awareness of hypoglycemia, through the putative effect of unsuspected recurrent episodes of nocturnal hypoglycemia. CONCLUSIONS In efforts to decrease the risk of nocturnal hypoglycemic episodes, various strategies can be used to minimize the nocturnal hyperinsulinemia that is associated with many insulin replacement regimens. Regular blood glucose monitoring (particularly at bedtime), the ingestion of appropriate bedtime snacks, and the utilization of short- and long-acting insulin analogues may all help to prevent or minimize the frequency of nocturnal hypoglycemia.