Diabetes mellitus is a major health problem due to its increasing prevalence and life-threatening complications. Antidiabetic sulfonylureas represent the first-line drugs in type 2 diabetes even though the most common associated risk is pharmacologically-induced hypoglycemia. In the development of this side effect are involved several factors including the pharmacokinetic and pharmacodynamic profile of the drug, patient age and behavior, hepatic or renal dysfunctions, or other drugs associated with a high risk of interactions. If all these are controlled, the risk-benefit balance can be equal to other oral antidiabetic drugs.