The group of beta-lactam compunds includes penicillins, cephalosporns, monobactams, carbapenems and ß-lactamase inhibitors. The basic structure of all these substances is a four-membered lactam ring. Betalactams are the most used antimicrobial drug sin the health care system of the Republic of Croatia, both in the form of outpatient as well as inpatient consumption. Allergy to betalactam antimicrobial drugs, specifically to penicillins, ranks first in the number of patient reports of all drugs used. New research shows that the exact number of betalactam allergies is much lower than the one reported. There is a number of consequences for the health system and the patient if a substitution drug is used instead of betalactam antimicrobial drugs when this is not needed. Some of these are an increase in antimicrobial resistance, a higher number of Clostridium difficile infections, an increase in hospital days, an increase in the number of admissions to intensive care unit, an increase in hospital readmissions and increased mortality. Given that all of the above impairs the quality of medical care for the patients, but also increases the cost for the healthy system, it is important to have tools that can quickly and efficiently detect hypersensitivity to betalactams. Patient hypersensitivity may present as an immediate reaction involving hypersensitivity mediated by IgE antibodies such as anaphlactic reaction or as delayed reactions that are usually milder in intensity but may also be life-threatening. A detail history of events describing hypersensitivity to betalactams may in some cases be sufficient to determine what reaction occured and whether there is a risk of subsequent betalactam intake. When the risk of an IgE-mediated reaction is identified, there is a reason to preform skin testing with penicillin antigen. An additional test may be a provocation test where the patient is exposed to the antigen of the drug and the patient's reaction is observed. There are also various in vitro tests to confirm the elements of cellular activation in hypersensitivity reactions but their specificity and sensitivity have not been sufficiently investigated in comparison to skin testing and provocation tests. If the patient is allergic to betalactams and these drugs are needed because there are no substitution drugs of equal quality for this indication, it is possible to perform desensitization which causes temporary tolerance to betalactams which would otherwise cause a hypersensitivity reaction.