The large scope of the human microbiome and its interactions with host tissues is currently unfolding. The complex interactions of the human microbiome with the human metabolome and epigenome may affect the susceptibility to and severity of complex diseases that include metabolic disorder, cancer and CNS disease states. In addition, the individual microbiome may modulate drug pharmacokinetics (PK) and pharmacodynamics (PD), contributing to drug response variations between individual patients. Current knowledge of such interactions represents only the tip of a very large iceberg. In the context of drug discovery and development, a notable aspect that deserves special attention is the study of microbiome-host interactions that impact the individual response to therapeutics.