Serious hypoglyoemia persists as a barrier for those who wish to reduce the chronic complications of diabetes rnellitus through tight glycemic control, especially for those with type 1 diabetes mellitus. Recent studies have shed new light on the pathophysiology of hypoglycemia unawareness and defective insulin counterregulation, both of which are crucial predisposing factors for serious hypoglycemia. Studies also indicate the importance of hypoglycemia and identify risk factors for hypoglycemia in different groups such as the elderly. With a better understanding of the mechanisms that underlie hypoglycemia unawareness, one hopes that treatments to avoid serious hypoglycemia will increasingly succeed. Renewed emphasis on treatment strategies should reduce the prevalence of hypoglycemia. Targeting therapies to prevent or reverse the defects leading to hypoglycemia unawareness and defective counter-regulation may help avoid the life- or brain-threatening damage that can result from hypoglycemia.