Both the Unified Microbiome Initiative (Alivisatos et al., Science, 2015) and the National Microbiome Initiative have emphasized the need to move beyond sequencing to better understand the fundamental molecular and chemical mechanisms that shape microbial communities in host and environmental habitats. Understanding the chemistry of microbiomes has broad implications, including providing functional annotations for the vast “dark matter” of microbial genomes, insights into the chemical languages that link microbes to each other and to their habitat, and translational implications for precision medicine, environmental health, and sustainable living. This symposium brings together scientists in biology and chemistry who rarely interact to address common questions. The interdisciplinary collaborations that result will profoundly accelerate basic microbiome research as well as help understand the role of the microbiome in human health and disease. We will emphasize speakers that employ innovative new methods and/or hypothesis-driven research to understand microbial systems at the molecular level. There is an emphasis on speakers with innovative paradigm-shifting research programs in chemistry, synthetic biology, genome editing, precision medicine, etc. Finally, many of the program speakers may not normally be invited to give talks at traditional microbiome conferences; instead the program features key innovators w ho are making significant and exciting contributions to this emerging field.