Despite human claims to superiority, it can be legitimately argued that microbes rule the world. Whether it is an ocean reef, a landfill, or a gastrointestinal tract, invisible communities of highly active and adaptable microbes prosper. Over time, mammalian species developed a symbiosis with microbes that are now important inhabitants not only in the intestines, but also in the mouth, skin, and vaginal tract. In the gut, commensal microbes are a critical element for the development of the gut-associated lymphoid tissue, pathogen resistance, nutrient digestion (fermentation), and intestinal epithelial cell gene expression. Proper balance is key, however, as microbial imbalances contribute to inflammatory bowel diseases, gastrointestinal cancers, and other intestinal disorders. Microbial colonization also plays a crucial role in oral disease, which is now the most common form of disease in dogs and cats. Recent evidence also suggests a role of intestinal microbiota on the metabolic phenotype and disease risk (e.g., obesity, metabolic syndrome) of the host. A significant hindrance to studying gut microbiota has traditionally been the inability to effectively identify and quantify microbial species. Researchers have been reliant upon microbial culturing methods that are not only laborious, time-consuming, and often inaccurate, but also greatly limited in scope. High-throughput, DNA-based methods have been developed recently and have changed the research environment dramatically. Recent experiments using these techniques have begun to characterize the identity and metabolic activity of the entire gastrointestinal microbiota and their association with health and disease. Despite this recent progress, more research is needed to provide deeper coverage of the oral and intestinal microbiomes, evaluate effects of age, genetics, or environment (e.g., diet) on its composition and activity, and identify its role in disease.