It is now appreciated that dendritic cells (DCs) play a primary role in oral tolerance and defense against mucosal pathogens. Specific DC subpopulations are localized to discrete regions within primary inductive tissues, like the Peyer's patch and mesenteric lymph node, and effector sites, like the lamina propria, and may have unique roles in driving regulatory, effector and memory T cell responses. Certain DC subpopulations may also help maintain T cell responses at sites of abnormal intestinal inflammation. While early in our understanding, knowledge about the involvement of DC subpopulations in the regulation of mucosal immunity may well provide a basis for the development of novel vaccines and therapeutics.