This lecture will explore one of the most widespread strategies on the planet – insect-bacteria mutualisms – using the tools of small molecule chemistry. Mutualisms, symbiotic relationships in which two partners reciprocally benefit from their association, dominate all realms of biology. Familiar examples include terrestrial plants and the mycorrhizal symbionts that provide them with inorganic compounds and trace elements or flowering plants and their pollinators. In the past few years, the laboratory has been exploring insect-bacteria mutualisms from a chemical and biochemical perspective. These mutualisms involve the interplay of an insect-bacteria mutualism, their predators, survival, and small molecules, and the role of small molecules and the genes that made them had received relatively little attention. The lecture will emphasize three simple lessons about these mutualisms: 1) they are widespread in the natural world, 2) real world symbioses involve multiple players, and 3) identifying the molecular basis these mutualisms provides a path to biologically important small molecules, their biosynthetic enzymes, and the evolution of resistance, sensitivity, and gene collectives. Examples will include: 1) the Southern pine beetle (SPB) system, 2) ambrosia beetle systems, 3) fungus-farming ants of the Neotropics, 4) mud daubers and honeybees, and possibly others.