Glyburide is an improved drug for the management of non-insulin-dependent diabetes mellitus (NIDDM). It is at least as effective as the first-generation oral hypoglycemics and is effective in doses that are considerably less than those needed with first-generation sulfonyl-ureas. While its mode of action is similar to that of other agents, glyburide has the unique feature of prolonged activity despite a short half-life and short duration in the body. Side effects are minimal, and toxic reactions have not been reported. While hypoglycemic episodes can occur, as with any blood glucose-lowering agent, they can be prevented by being alert to patients who may be more sensitive to oral agents. Unlike older sulfonylureas, about 50% of glyburide is excreted through the feces. In 14 years of worldwide experience, glyburide has rarely shown disulfiram-like effects and has not shown antidiuretic effects. While glyburide produces an insulin release response to glucose that parallels a normal physiological response, it appears to also decrease resistance to insulin and sensitize the receptors while utilizing the patient's available endogenous insulin. There are two major metabolites, but they are inert and are rapidly excreted, having no hypoglycemic effect. Considering the safety of glyburide and the large worldwide population that uses this agent, it is expected that this new second-generation hypoglycemic agent will greatly increase the therapeutic spectrum for NIDDM. Not only is it possible for more patients with diabetes to be treated, but many already being treated orally can achieve better regulation with this effective new oral agent.