Genes, bacteria, and immunity contribute to the pathogenesis of inflammatory bowel disease. Most genetic risk relates to defective sensing of microbes and their metabolites or defective regulation of the host response to the microbiota. Because the composition of the microbiota shapes the developing immune system and is determined in early life, the prospect of therapeutic manipulation of the microbiota in adulthood after the onset of disease is questionable. However, the microbiota may be a marker of risk and a modifier of disease activity and a contributor to extraintestinal manifestations and associations in some patients with inflammatory bowel disease.