Antibiotics are drugs indicated to treat bacterial infections. The clinical use of antibiotics is considered as one of the greatest medical achievements of the 20th century. According to the World Health Organization, rational pharmacotherapy means that the patients receive the appropriate medicines, for appropriate indications, in doses that meet their own individual requirements, for an adequate period of time, at the lowest cost both to them and the society. Inappropriate use of antibiotics is one of the main causes of antimicrobial resistance. It occurs as the result of inadequate education of the general population and health professionals, procurement of over-the-counter antibiotics without appropriate physician diagnoses, lack of adherence, self-medication with antibiotic residues, promotion of pharmaceutical companies, lack of adequate rapid tests to directly prove the cause and pressure from patients. Bacterial resistance to antibiotics can be primary and secondary. Mechanisms of secondary resistance are the production of enzymes that alter the structure of antibiotics, changes of the permeability to drugs, modification of the receptor molecule for antibiotics and enhancement od the ejection of antibiotics from the cell by efflux pumps. Multidrug-resistant bacteria are Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Enterobacter spp. and Pseudomonas aeruginosa. Bacterial susceptibility to antibiotics is determined by antibiogram. Some of the methods are dilution method, disk diffusion method, E-test, breakpoint method and methods of proving enzymes or resistance genes. Measures to limit antimicrobial resistance are timely and adequate education of the general population and health professionals, prevention of self-medication with antibiotics, regular monitoring of antimicrobial drug consumption and resistance rates and investment in research for the purpose of making new antibiotics with innovative mechanisms of action.