The emergence and spread of antibiotic resistance among pathogenic bacteria pose a significant threat to public health. The reservoir of antibiotic resistance genes (ARGs), known as the resistome, includes not only clinical pathogens but also commensal and environmental bacteria, as well as mobile genetic elements and bacteriophages. Horizontal gene transfer (HGT) is a key mechanism for the dissemination of ARGs, with conjugation being the most influential. Transformation and transduction are less prominent but may play a larger role than previously thought. Understanding the extent of the resistome and its mobilization to pathogenic bacteria is crucial for controlling the spread of antibiotic resistance. This review discusses the concept of the resistome, provides examples of HGT of clinically relevant ARGs, and presents an overview of the contributions of various HGT mechanisms to the spread of antibiotic resistance.The emergence and spread of antibiotic resistance among pathogenic bacteria pose a significant threat to public health. The reservoir of antibiotic resistance genes (ARGs), known as the resistome, includes not only clinical pathogens but also commensal and environmental bacteria, as well as mobile genetic elements and bacteriophages. Horizontal gene transfer (HGT) is a key mechanism for the dissemination of ARGs, with conjugation being the most influential. Transformation and transduction are less prominent but may play a larger role than previously thought. Understanding the extent of the resistome and its mobilization to pathogenic bacteria is crucial for controlling the spread of antibiotic resistance. This review discusses the concept of the resistome, provides examples of HGT of clinically relevant ARGs, and presents an overview of the contributions of various HGT mechanisms to the spread of antibiotic resistance.