Purpose of Review <p>Complex interactions between gut microbiota and various drugs can significantly influence drug pharmacokinetics. We examined recent <i>in vitro</i>, <i>ex vivo</i>, and <i>in vivo</i> studies to understand how microbiota directly influences drug metabolism and absorption in order to inform future research and clinical practice.</p> Recent Findings <p>Considerable progress has been made for multiple drug classes using in vitro anaerobic culturing assays and ex vivo systems with human fecal communities, as well as animal models that have provided insights into both direct microbial metabolism of drugs and indirect host-microbiota interactions via regulation of host enzymes or transporters. However, how these effects impact clinical pharmacokinetics remains poorly defined.</p> Summary <p>Future progress will depend on the development of experimental and computational tools to integrate microbiota data into pharmacokinetic modeling and drug development. A mechanistic understanding of microbiota-mediated drug metabolism is critical for improving predictions of drug efficacy, safety, and personalized dosing strategies.</p>