This chapter focuses on the entire concept of absorption, distribution, metabolism, and excretion, which is fundamental to toxicology and pharmacology, yet the influence of the microbiome, has been ignored. Smoking, inflammatory diseases, use of probiotics, aging, obesity, and inflammatory diseases also significantly influence the composition of microbiome populations. The most obvious ways a host can affect their microbiota is by dietary change. The gut bacteria are extremely important in the metabolism of orally ingested xenobiotics. Bacteria do have defined functions in the human gastrointestinal tract, such as vitamin synthesis, metabolism of carcinogens and toxicants, formulation of non-digestible dietary residues, and fortification of barriers. A review of common laboratory animal species determined that some 500–1000 species may inhabit their intestines and that these complex populations are in a subtle state of homeostasis unless their environment is altered. Short-term and long-term, acutely or chronically, the microbiota influences the absorption of xenobiotic compounds.