Penicillin allergy is the most commonly reported drug allergy in the United States. Although penicillin allergy is widely reported, 80% to 90% of individuals with self-reported penicillin allergy are actually able to tolerate penicillins after undergoing evaluation for penicillin allergy. Because most patients with self-reported penicillin allergy will have subsequent negative allergy testing results and tolerate penicillins, they may be unnecessarily exposed to broader-spectrum antibiotics. Use of such antibiotics leads to increased risks of developing antibiotic-resistant microorganisms and incur higher health care utilization costs. In this article, we provide an overview of penicillin allergy and its clinical manifestations as well as an approach for the evaluation and management of penicillin allergy.