The role of microplastics (MPs) in the spread of antibiotic resistance genes (ARGs) is increasingly attracting global research attention due to their unique ecological and environmental effects. The ubiquitous use of plastics and their release into the environment by anthropic/industrial activities are the main sources for MP contamination, especially of water bodies. Because of their physical and chemical characteristics, MPs represent an ideal substrate for microbial colonization and formation of biofilm, where horizontal gene transfer is facilitated. In addition, the widespread and often injudicious use of antibiotics in various human activities leads to their release into the environment, mainly through wastewater. For these reasons, wastewater treatment plants, in particular hospital plants, are considered hotspots for the selection of ARGs and their diffusion in the environment. As a result, the interaction of MPs with drug-resistant bacteria and ARGs make them vectors for the transport and spread of ARGs and harmful microorganisms. Microplastic-associated antimicrobial resistance is an emerging threat to the environment and consequently for human health. More studies are required to better understand the interaction of these pollutants with the environment as well as to identify effective management systems to reduce the related risk.