Purpose of Review: Thriving microbiome research for the past few years is providing new insights into biological mechanisms guiding human health and/or disease states. In this review, we will highlight the recent literature providing further evidence for the central role that the microbiota plays in association with the human host. Recent Findings: The host microbiota, both bacteria and fungi, with their collective genome (metagenome) and metabolites (metabolome) play a key role in health and disease states. We now have enough evidence that there are strong relationships and multidirectional interactions between the human host and the commensal bacterial, fungal, and viral inhabitants. Summary: Microbiome research has been at the forefront of research as a potential future target for precision medicine with the development of novel diagnostic assays and treatment approaches. Ongoing investigations are still unraveling the mechanisms by which such organisms contribute to health and disease.