The pathogenesis of inflammatory bowel disease (IBD) is complex and involves both innate and adaptive immune responses. This article addresses, in a selective and speculative fashion, the topic of how the various components of the intestinal innate immune system can be manipulated for the purpose of developing new therapeutic approaches. These various components include: agents that stimulate mucosal innate immune responses, such as food components and the gut microbiota; cells that directly respond to these stimuli, including epithelial cells, macrophages and dendritic cells; and molecules that mediate innate immune responses, such as Toll-like receptors and protein kinases. Downregulation of excessive innate immune responses makes therapeutic sense in both pediatric and adult IBD. However, because IBD is complex and characteristically chronic, major alterations of adaptive immunity are also involved in the mediation of inflammation. Thus, novel and truly effective approaches to treat IBD will undoubtedly require intervening in the innate as well as the adaptive branches of the mucosal immunity.