Аннотация: Antibiotic resistance (AR) poses a serious global health threat that undermines the efficacy of antimicrobial therapies in both human and veterinary medicine. Since the advent of antibiotics, their misuse and overuse have accelerated the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacterial strains. This review explores the molecular and genetic mechanisms of antibiotic resistance, including enzymatic degradation, efflux pump activity, target modification, and horizontal gene transfer. It further discusses the physiological consequences of resistant infections, which include prolonged illness, increased mortality, and reduced treatment options in humans and animals alike. Transmission pathways such as human-to-human contact, zoonotic transmission from livestock and companion animals, and environmental contamination underscore the interconnectedness of antibiotic resistance across ecological systems. From a One Health perspective, the paper highlights the urgent need for integrated strategies, including antimicrobial stewardship, infection prevention, and the development of alternative therapies like bacteriophages, antimicrobial peptides, and probiotics. Addressing antibiotic resistance requires a coordinated, multidisciplinary approach that spans public health, veterinary science, agriculture, and environmental management to mitigate this growing crisis and preserve the efficacy of life-saving antimicrobial agents.