The dissemination of antimicrobial resistance (AMR) in microbial ecosystems is primarily driven by horizontal gene transfer (HGT), which allows bacteria to acquire resistance genes (ARGs) from various sources. This process involves three main mechanisms: conjugation, transformation, and transduction. Conjugation, facilitated by plasmids or integrative elements, is the most common and efficient method for spreading ARGs, especially among pathogenic bacteria. Transformation, where bacteria take up naked DNA from the environment, and transduction, involving bacteriophages transferring bacterial DNA, also contribute, though less so than conjugation. Gene transfer agents (GTAs), which are bacteriophage-like particles, can also transfer genetic material, including ARGs, between bacteria. The resistome, encompassing all ARGs in an ecosystem, is a vast reservoir of resistance genes that can be mobilized to pathogens. Environmental exposure to antibiotics, particularly through agricultural and medical use, increases the selection pressure for resistant strains, leading to the spread of ARGs in various ecosystems. The resistome is increasingly recognized as a critical factor in the global AMR crisis, with ARGs found in soil, wastewater, and the human gut microbiome. Understanding the mechanisms of HGT and the role of the resistome is essential for developing strategies to control the spread of antibiotic resistance. This review highlights the importance of HGT in the dissemination of ARGs and the need for further research into the resistome's role in microbial ecosystems.The dissemination of antimicrobial resistance (AMR) in microbial ecosystems is primarily driven by horizontal gene transfer (HGT), which allows bacteria to acquire resistance genes (ARGs) from various sources. This process involves three main mechanisms: conjugation, transformation, and transduction. Conjugation, facilitated by plasmids or integrative elements, is the most common and efficient method for spreading ARGs, especially among pathogenic bacteria. Transformation, where bacteria take up naked DNA from the environment, and transduction, involving bacteriophages transferring bacterial DNA, also contribute, though less so than conjugation. Gene transfer agents (GTAs), which are bacteriophage-like particles, can also transfer genetic material, including ARGs, between bacteria. The resistome, encompassing all ARGs in an ecosystem, is a vast reservoir of resistance genes that can be mobilized to pathogens. Environmental exposure to antibiotics, particularly through agricultural and medical use, increases the selection pressure for resistant strains, leading to the spread of ARGs in various ecosystems. The resistome is increasingly recognized as a critical factor in the global AMR crisis, with ARGs found in soil, wastewater, and the human gut microbiome. Understanding the mechanisms of HGT and the role of the resistome is essential for developing strategies to control the spread of antibiotic resistance. This review highlights the importance of HGT in the dissemination of ARGs and the need for further research into the resistome's role in microbial ecosystems.