Beside beta-lactams, sulfonamide antibiotics are among the most common causes of drug allergy. Hypersensitivity to sulfonamides including IgE-mediated immediate, delayed cell-mediated mechanisms, and severe life-threatening reactions are still incompletely understood. Unfounded concerns of cross-reactivity between sulfonamide antibiotics and a variety of non-antibiotic-containing sulfonamide drugs render pharmacotherapy unnecessarily difficult. Here, the history, clinical manifestations, diagnosis and treatment of sulfonamide allergy are briefly reviewed.