Rapid-acting insulin analogues were developed in answer to the need for a more appropriate time-action profile for prandial insulin substitution therapy. Improvements in at least one of three important endpoints needs to be demonstrated-metabolic control, hypoglycemic events, and/or quality of life-if there is to be a case for use of a new insulin preparation. This paper considers the data available on hypoglycemic events in the 24 controlled clinical trials (19 open, unblinded, and 5 double-blind) reported to date with rapid-acting insulin analogues (22 studies with insulin lispro). A significant reduction in the incidence of mild hypoglycemia was observed in 5 of 22 studies (22%). No change in frequency of severe hypoglycemic episodes was observed 10 of 12 studies (83%) reporting such events. A decrease in the frequency of nocturnal hypoglycemia has been reported in six studies; however, in the other 18 studies, no similar decrease in numbers were reported. There is no evidence for a reduction in patient awareness of hypoglycemia with rapid-acting insulin analogues. Even a slight reduction in hypoglycemic events would be welcomed by diabetic patients. However, rapid-acting insulins are only appropriate for use in patients using an intensive insulin regimen. Such patients are well motivated and well educated and will be able to adapt their insulin therapy to take account of the changes in the time-action profile of the rapid-acting insulin analogues. Thus, rapid-acting insulin analogues do not appear to have revolutionized insulin therapy, but appropriate use should result in benefits such as improved metabolic control for diabetic patients.