Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on health. The large genetic and enzymatic repertoire carried out by gut microbial communities provides them with the ability to affect the therapeutic efficacy, toxicity and pharmacokinetic parameters of many chemicals. The gut microbiome is a promising source of drug targets and noninvasive biomarkers, for the early detection of diseases and personalised medicine against cancer. A large number of animal species, including humans, have evolved to feed on toxic or indigestible plants by carrying xenobiotic-degrading microbial communities. Vertical transmission of gut microbiome metabolic capabilities to future generations could even be a mode of transgenerational inheritance. Changes in human gut microbiome composition have been implicated in a wide range of clinical conditions, some of which develop locally in the intestine, such as Crohn's disease, but many others occurring at distant sites, such as metabolic diseases. Recent advances in next-generation sequencing have opened new avenues to determine the role of microbiomes in the toxicity of chemicals, expanding the field of genomic toxicology to a broader metagenomic toxicology research area. In this review, we present key gut microbiome research areas, with a focus on metabolism of xenobiotics by the gut microbiome.