<p>Antibiotic resistance is a significant issue in modern infectious medicine and veterinary science, with animals, including horses, playing a crucial role in its dissemination. Antibiotics, used both for treatment and prevention of diseases in animals, influence the composition of the microbiota and promote the selection of resistant strains that can be transmitted to humans through direct or environmental contact. Horses, currently classified as companion animals, serve as a reservoir of commensal and pathogenic bacteria, including multidrug-resistant strains capable of horizontal gene transfer. Of particular importance are plasmids and integrons that carry genes encoding β-lactamases, which significantly reduce the effectiveness of therapy in both humans and animals. Analysis of the equine oral and gut microbiota highlights the potential of these environments as sources and vectors of resistance. Understanding the mechanisms underlying the transfer and persistence of resistance genes in horses is crucial for public health and helps define new directions for research within the One Health framework.</p>