Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.