The diversity and significance of host-associated microbial communities has emerged over the last 15 years to the point when some may now assume that “Nothing in Biology makes sense except in the light of the microbiome”. The advent of high-throughput ‘omics’ techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment, and has radically changed our views of biology, evolution and individuality. Sit at the interface between a host and its environment, the microbiome is a dynamic interface that responds to both host and environmental factors, for better or worse. For this reason, the microbiome now appears as a relevant, yet understudied compartment for ecotoxicology research. Various examples show that the microbiome reacts to and interacts with contaminants, with consequences for hosts and the ecosystem, and great advances can be expected from studies in which microbiome research meets toxicology. Yet, for the encounter to be scientifically productive, caution is needed in study design, inferences and extrapolations. In this paper, we emphasize the relevance and challenges of microbiome research in environmental toxicology through documented examples, and draw readers attention to pitfalls that should not be overlooked when producing and analyzing their data. We advocate for the development of a “microbiome-aware ecotoxicology”.