Our bodies each possess a unique and dynamic collection of microbes and viruses, collectively the "microbiome", with distinct metabolic capacities from our human cells. Unforeseen modification of drugs by the microbiome can drastically alter clinical effectiveness, in the most dramatic cases leading to fatal drug interactions. Pharmaceuticals can be activated, deactivated, toxified, or release metabolites that alter the "canonical" pharmacokinetics of the drug. Predicting and characterizing microbe-drug interactions is thus necessary to develop and implement personalized drug administration protocols and, more broadly, to improve drug safety and efficacy. This review focuses on microbiome driven alterations to drug pharmacokinetics and provides a research framework for pharmacologists interested in characterizing microbiome interactions with any drug of interest.