Background <p>The fish microbiome is increasingly recognized as an important factor influencing host responses to xenobiotics, although its role remains largely associative and is still being elucidated. The composition and functional capacity of fish microbiomes are shaped by environmental stressors, diet and pollution, which can alter microbial communities and potentially influence the host’s ability to process xenobiotic exposure.</p> Main text <p>Recent advances in microbial ecology and toxicology suggest that gut and skin microbiota are involved in the biotransformation of xenobiotics, potentially modulating their toxicity. These effects are mediated in part through microbial enzymatic activities, including those of azoreductases, β-glucuronidases and cytochrome P450-like enzymes, which catalyze reductive, hydrolytic and oxidative reactions that can alter xenobiotic bioavailability and activity. In addition, microbiome-host interactions may influence immune responses and metabolic pathways, contributing to the detoxification or bioactivation of xenobiotics. Environmental contaminants can also disrupt microbial composition and function, leading to dysbiosis, which may affect toxicokinetic processes and host susceptibility. However, the underlying molecular mechanisms and their relevance across fish species remain insufficiently understood.</p> Conclusions <p>This review synthesizes current knowledge on interactions between the fish microbiome and xenobiotics, highlighting mechanistic insights, ecological implications and existing knowledge gaps. It also discusses how microbiome dysbiosis may influence contaminant exposure and ecotoxicological outcomes in fish. Although this emerging field offers promising perspectives, its application remains limited by insufficient mechanistic and species-specific evidence. Further integrative studies are needed to clarify these interactions and support their incorporation into ecotoxicological risk assessment and environmental management.</p>