β-lactams are the most widely used antibiotic family, but they are also the most common cause of drug‑induced hypersensitivity reactions. The estimated prevalence of reported penicillin allergy ranges between 9% and 12%, although a high percentage of patients with a history of penicillin allergy have no subsequent reactions on reexposure to β-lactams. A self‑reported penicillin allergy has been associated with antimicrobial resistance, increased cost, intensive care admission, and death, making it essential to establish an accurate diagnosis. In addition to a thorough clinical history, diagnostic methods include skin tests, in vitro tests, and drug‑challenge tests. In this review, the diagnosis and management of patients with self‑reported penicillin allergy is discussed, including the recently introduced antimicrobial stewardship strategy.