Purpose of review The microbiome continues to demonstrate an important role in immune and metabolic programming. This review will focus on the mechanistic implications of recent findings for diabetes pathogenesis and treatment. Recent findings Multiple techniques are developing to specify the microbiome. At the same time, new insights have emerged into local interactions of microbial products with human development. New findings demonstrate that key bacteria and their products result in the programming of diabetes-modulating Th17 and regulatory T lymphocytes within and outside the intestine. The role of the bacterial metagenome in programming human metabolism has also revealed new insights. In turn, these findings suggest a framework in which the microbiome may be modified to change the course of diabetes. Summary The microbiome is a key regulator of metabolism and immunity. Specific bacteria and their secreted products are now known to program Th17 and regulatory T-cell development, which may change the course of diabetes. Bacterial genomics are demonstrating important, modifiable roles of bacterial gene products in metabolism. Further understanding of this symbiotic relationship will provide new avenues for intervention in diabetes.