Summary: Drug hypersensitivity reactions represent 15% of all adverse drug reactions and affect more than 7% of the general population. Penicillins and cephalosporins are a commonly used group of beta-lactam antibiotics, most often causing drug-induced allergic reactions. The diagnosis of adverse reactions after antibiotics is a big challenge in everyday clinical practice due to the very diverse clinical picture and many coexisting factors. The basic diagnostic tools are accurate interview, in vivo tests, in vitro tests and provocation test with the suspected drug in a hospital setting. Despite quite advanced diagnostic methods, the mechanism of undesirable drug reactions still remains unexplained in many cases, and the recognition of a drug allergy remains an art.