Background: Since its discovery in the early 1980s, Helicobacter pylori has been linked to a variety of gastric and extragastric diseases. Chronic infection with H. pylori causes histologically evident gastritis in all colonized individuals and is the predominant risk factor for gastric and duodenal ulcers as well as gastric adenocarcinoma. However, increasingly robust experimental and epidemiological evidence suggests that H. pylori may at the same time be beneficial to its carriers, as it efficiently prevents allergic disorders and chronic inflammatory conditions. The purpose of this review is to summarize and document the latest evidence for a possible inverse association of H. pylori infection status and the risk of inflammatory bowel disease (IBD), as provided in both experimental and human observational studies. The pathogenesis of IBDs, the available mouse models for these diseases and the dual role of H. pylori in health and disease are presented in dedicated chapters. Summary and Key Messages: Almost all available epidemiological data suggest that H. pylori infection is inversely associated with both Crohn's disease (CD) and ulcerative colitis in European, Asian as well as American populations; large meta-analyses reviewing 30 original articles or more document that this inverse association is especially strong in CD patients and in children and young adults. Experimental data available from various mouse models of IBD confirm that live H. pylori infection as well as treatment with immunomodulatory molecules of H. pylori reduce clinical and histopathological IBD symptoms. Various proposed mechanisms involving the tolerization of dendritic cells, the production of protective cytokines and the preferential induction and differentiation of regulatory T-cells are presented. The implications of the beneficial aspects of the Helicobacter-host interaction for H. pylori eradication decisions, as well as potential new therapeutic options in the treatment of IBD are discussed in this review.