The idiopathic inflammatory bowel diseases, broadly classified as either Crohn's disease or ulcerative colitis, are caused by a dysregulated mucosal immune response to a luminal antigen, possibly a bacterium, in a genetically predisposed host. A rapid expansion of knowledge in recent years has greatly increased our understanding of the pathophysiology of these disorders. For example, the relatively recent discovery of the NOD2 gene, a protein involved in bacterial sensing, has provided further evidence of the complex interplay between hosts and microbes in Crohn's disease. Significant recent advances have also occurred with the discovery of the role of Toll-like receptors and dendritic cells in the development of gut inflammation, and the role of proinflammatory cytokines in the development and potentiation of gut inflammation. This article presents an update on these key developments and emphasizes the translational aspects of research that are directly related to patient care.