The United Kingdom Prospective Diabetes Study shows sulfonylureas to be an effective first-line therapy for people with type 2 diabetes mellitus. The durability of the glycemic control obtained is dependent on the degree to which beta-cell function can be maintained, but sulfonylureas appear neither to increase nor to decrease the underlying rate of loss of beta-cell function. As sulfonylureas act by enhancing insulin secretion, they are probably best used close to the time when diabetes is diagnosed when beta-cell function is at its greatest and their utility can be extended by judicious use in combination with agents that improve glycemia by different modes of action, including insulin.