The spatial organization of complex natural microbiomes is critical to understanding the physiology and ecology of microbial communities as well as their interaction with their host and their impact on both health and disease. Although next-generation DNA sequencing technology and metagenomics have revolutionized the analysis of microbial communities, a major gap in our understanding is the lack of spatial information at the micron level. Using spectral imaging fluorescence in situ hybridization as guided by tagged sequence analysis, we have discovered distinctive, multi-genus consortia in the human oral microbiome. The spatial structure of the consortia reveals unanticipated interactions and provides a framework for understanding the organization, metabolism, and systems biology of the microbiome, and ultimately its effect on the health of the human host. Our synthesis of high-throughput sequencing data with spatial and structural information demonstrates the informative value of microbial biogeography at the micron scale.