A TP-sensitive potassium (K_ATP) channels, so named because they are inhibited by intracellular _ATP, play key physiological roles in many tissues. In pancreatic β cells, these channels regulate glucose-dependent insulin secretion and serve as the target for sulfonylurea drugs used to treat type 2 diabetes. This review focuses on insulin secretory disorders, such as congenital hyperinsulinemia and neonatal diabetes, that result from mutations in K_ATP channel genes. It also considers the extent to which defective regulation of K_ATP channel activity contributes to the etiology of type 2 diabetes.