Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.