Beta-lactam antibiotics are the cornerstone of most of the severe bacterial infections. However, their use can be limited by resistances and allergic reactions. Allergic reactions to beta-lactam antibiotics account for only a small proportion of reported adverse drug reactions, but they are related with an important morbidity, mortality and increase of the health care costs. Drug-specific IgE antibodies cause early reactions, whereas T cells play a predominant role in delayed hypersensitivity reactions. For penicillin a major antigenic determinant and several minor determinants have been identified. Clinical assessment is mandatory by medical history, skin and other testing, including provocation. If the beta-lactam should be avoided or a desensitization procedure should be performed depends on the nature and severity of the reaction. Several new antibiotics are currently available (tigecycline, linezolid, daptomycin, etc.) that are as effective and safe as beta-lactams. In this article we have developed a few recommendations for the management of patients with allergy to beta-lactams on the basis of evidence and expert opinion.