Currently available oral agents for the treatment of type 2 diabetes mellitus include a variety of compounds from 5 different pharmacologic classes with differing mechanisms of action, adverse effect profiles, and toxicities. The oral antidiabetic drugs can be classified as either hypoglycemic agents (sulfonylureas and benzoic acid derivatives) or antihyperglycemic agents (biguanides, alpha-glucosidase inhibitors, and thiazolidinediones). In this review, a brief discussion of the pharmacology of these agents is followed by an examination of the adverse effects, drug-drug interactions, and toxicities. Finally, treatment of sulfonylurea-induced hypoglycemia is described, including general supportive care and the management of pediatric sulfonylurea ingestions. The adjunctive roles of glucagon, diazoxide, and octreotide for refractory hypoglycemia are also discussed.