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Crohn's disease and ulcerative colitis, the 2 major forms of inflammatory bowel disease (IBD) in humans, arise in genetically predisposed individuals because of an abnormal immune response direct against constituents of the gut flora. Defects in counter-regulatory mechanisms are supposed to amplify and maintain the IBD-associated mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory pathways in the gut could contribute to halt the IBD-associated tissue-damaging immune response. Various suppressive T cell (Tregs) subsets have been characterized phenotypically and functionally and over the last decade, there has been enormous effort for optimizing the procedures for the in vitro expansion/generation of these cells for therapeutic purposes. Here we review the mechanisms of action and functional relevance of Tregs in the maintenance of gut inflammation and analyze the available data about the use of these cells in the treatment of IBD patients.