Here, we review the possible reasons responsible for the occurrence, maintenance and proliferation of antibiotic resistance genes (ARGs) in the environment, as well as the corresponding mechanisms of their development, diffusion and transfer. Additionally, elimination strategies are also discussed. The factors that influence the development of ARGs are selection pressure, including that from antibiotics, metal and multiple other factors, co-resistance and cross-resistance, microbial consortium structure, nutrients in the environment and oxidative stress responses. Process parameters, transport pathways, and elimination strategies to reduce the health risk caused by ARGs are also reviewed in detail. Moreover, knowledge gaps and future opportunities of ARGs are addressed.