Among patients with a reported history of penicillin allergy, 80% to 90% have no evidence of IgE antibodies to penicillin on skin testing and thus avoid penicillin unnecessarily. Moreover, 97% to 99% of such patients with a penicillin skin test negative to the major and minor determinants can tolerate penicillin without risk of an immediate-type hypersensitivity reaction. A penicillin skin test is valuable for evaluating penicillin allergy in patients who need penicillin or cephalosporin. Assessment of sensitivities to penicillin is important to reduce the unnecessary use of antimicrobial agents such as vancomycin. We review the role of penicillin skin testing for evaluating penicillin allergy and the use of cephalosporin in patients with a history of penicillin allergy.