The environment is increasingly recognized as a hotspot for the selection and dissemination of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria. Non-antibiotic agents, such as metals, biocides, plant protection products (PPPs), and non-antibiotic drugs (NADs), can co-select for antibiotic resistance through mechanisms like co-resistance, cross-resistance, and co-regulation. This review summarizes the co-selective effects of these agents in the environment, highlighting their potential to increase antibiotic resistance in bacteria. Antibiotic resistance (AMR) is a global health concern, with predictions that it could lead to 10 million deaths annually by 2050. Antibiotic resistance can be acquired through de novo mutation or horizontal gene transfer (HGT) of ARGs. Co-selection, the simultaneous selection for resistance to multiple agents, can occur through genetic linkage, shared resistance mechanisms, or coordinated regulatory responses. Metals, biocides, NADs, and PPPs can co-select for antibiotic resistance by increasing HGT rates, promoting the expression of resistance genes, and altering bacterial physiology. For example, metals can co-select for antibiotic resistance through genetic linkage or shared resistance mechanisms. Biocides, such as quaternary ammonium compounds (QACs), can co-select for antibiotic resistance through co-resistance or cross-resistance. NADs, including chemotherapeutic agents, can increase HGT rates and promote the expression of resistance genes. PPPs, such as herbicides, fungicides, and insecticides, can also co-select for antibiotic resistance by increasing ARG abundance and altering microbial communities. The environment is a significant reservoir of ARGs, and exposure to selective agents can increase resistance in bacteria. The presence of these agents in the environment can lead to the selection and dissemination of ARGs, which can then be transmitted to humans through food, water, or direct contact. The concentrations of these agents can vary widely, and subinhibitory concentrations can amplify resistance or increase persistence of resistance. There are significant knowledge gaps in understanding the co-selective effects of these agents in the environment, particularly in terms of their mechanisms, concentrations, and environmental contexts. Further research is needed to address these gaps and to develop strategies for mitigating the spread of antibiotic resistance. The complexity of chemical interactions, including their potency, behavior, and environmental factors, must be considered in future studies. Additionally, the effects of these agents in complex microbial communities and the interactions between different agents need to be investigated to better understand their co-selective potential.The environment is increasingly recognized as a hotspot for the selection and dissemination of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria. Non-antibiotic agents, such as metals, biocides, plant protection products (PPPs), and non-antibiotic drugs (NADs), can co-select for antibiotic resistance through mechanisms like co-resistance, cross-resistance, and co-regulation. This review summarizes the co-selective effects of these agents in the environment, highlighting their potential to increase antibiotic resistance in bacteria. Antibiotic resistance (AMR) is a global health concern, with predictions that it could lead to 10 million deaths annually by 2050. Antibiotic resistance can be acquired through de novo mutation or horizontal gene transfer (HGT) of ARGs. Co-selection, the simultaneous selection for resistance to multiple agents, can occur through genetic linkage, shared resistance mechanisms, or coordinated regulatory responses. Metals, biocides, NADs, and PPPs can co-select for antibiotic resistance by increasing HGT rates, promoting the expression of resistance genes, and altering bacterial physiology. For example, metals can co-select for antibiotic resistance through genetic linkage or shared resistance mechanisms. Biocides, such as quaternary ammonium compounds (QACs), can co-select for antibiotic resistance through co-resistance or cross-resistance. NADs, including chemotherapeutic agents, can increase HGT rates and promote the expression of resistance genes. PPPs, such as herbicides, fungicides, and insecticides, can also co-select for antibiotic resistance by increasing ARG abundance and altering microbial communities. The environment is a significant reservoir of ARGs, and exposure to selective agents can increase resistance in bacteria. The presence of these agents in the environment can lead to the selection and dissemination of ARGs, which can then be transmitted to humans through food, water, or direct contact. The concentrations of these agents can vary widely, and subinhibitory concentrations can amplify resistance or increase persistence of resistance. There are significant knowledge gaps in understanding the co-selective effects of these agents in the environment, particularly in terms of their mechanisms, concentrations, and environmental contexts. Further research is needed to address these gaps and to develop strategies for mitigating the spread of antibiotic resistance. The complexity of chemical interactions, including their potency, behavior, and environmental factors, must be considered in future studies. Additionally, the effects of these agents in complex microbial communities and the interactions between different agents need to be investigated to better understand their co-selective potential.