About 10-15% of all adults report that they are allergic to penicillin or other antibiotics, although the accuracy and significance of these reports remain unclear. In the outpatient setting, clinicians often face a dilemma in prescribing for patients with a history of an allergic reaction to antibiotics. Which drugs should these patients avoid? Are these patients at increased risk for an allergic reaction to related drugs? This Issue Brief summarizes several large studies that can help guide and improve the management of patients with antibiotic allergies.