Inflammatory bowel disease (IBD) is thought to develop as a result of interactions between environmental, microbial and immune-mediated factors in a genetically susceptible host. The role of the microbiome in the development, progression and treatment of IBD has been a subject of considerable interest. Studies have shown that the gut microbiome is different in patients with IBD compared with healthy control subjects. Mutations have been identified in genes that are involved in microbiome-immune interactions in patients with IBD. Epidemiologic observations implicate such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation and diet in the pathogenesis of IBD. In the Journal of Allergy and Clinical Immunology, we discuss the role of the gut microbiome in patients with IBD.