The resistance of bacteria to antimicrobial substances is one of the most serious epidemiological problems present on a global scale. The widespread use of same classes of antimicrobials in human and veterinary medicine, often without laboratory confirmation of the efficacy of active compounds used, contributes to the selection of resistant bacteria in humans and animals, and their spread in nature. The increasing resistance of pathogenic bacteria leads to serious consequences for both human and animal health. However, the resistance of commensal bacteria is equally important as they constitute a reservoir and vector of resistance determinants in the environment. Exposure to antimicrobials belonging to different classes can lead to cross-resistance and the selection of genes that may spread horizontally on mobile genetic elements. The emergence of plasmid-encoded resistance to critically important antibiotics for human medicine e.g. carbapenems or polymyxins is alarming. On the example of antibiotics classified as critically important for human medicine, it is possible to discuss almost all bacterial mechanisms of antimicrobial resistance. For effective combat against the growing antibiotic resistance of bacteria, it is necessary to know the mechanisms of resistance and the methods of their acquisition by bacteria. The aim of the paper is to review the ways that critically important antimicrobials act on bacterial cells and present complex mechanisms that are responsible for resistance to these substances as well as genes conferring for resistance.