The human gut microbiome is considered critical for establishing and maintaining intestinal function and homeostasis throughout life. Evidence for bidirectional communication with the immune and nervous systems has spawned interest in the microbiome as a key factor for human and animal health. Consequently, appreciation of the microbiome as a target of xenobiotics, including environmental pollutants such as heavy metals, has risen steadily because disruption of a healthy microbiome (dysbiosis) has been linked to unfavorable health outcomes. Thus, toxicology must consider toxicant effects on the host's microbiome as an integral part of the holobiont. We discuss current findings on the impact of toxic metals on the composition, diversity, and function of the gut microbiome as well as the modulation of metal toxicity by the microbiome. Present limitations and future needs in elucidating microbiome-metal interactions and the potential of harnessing beneficial traits of the microbiota to counteract metal toxicity are also considered.