Gut-resident forkhead box P3 (FOXP3)(+)CD4(+) regulatory T cells (Treg cells) are distinct from those in other organs and have gut-specific phenotypes and functions. Whereas Treg cells in other organs have T cell receptors (TCRs) specific for self antigens, intestinal Treg cells have a distinct set of TCRs that are specific for intestinal antigens, and these cells have pivotal roles in the suppression of immune responses against harmless dietary antigens and commensal microorganisms. The differentiation, migration and maintenance of intestinal Treg cells are controlled by specific signals from the local environment. In particular, certain members of the microbiota continuously provide antigens and immunoregulatory small molecules that modulate intestinal Treg cells. Understanding the development and the maintenance of intestinal Treg cells provides important insights into disease-relevant host-microorganism interactions.