Helicobacter pylori is an etiologic agent of chronic gastritis, peptic ulcer disease, and gastric carcinogenesis in humans. Infection with H. pylori is common, with prevalence rates varying between 20% and 90%, depending on the population surveyed. Vigorous immune responses to H. pylori are observed in infected individuals, yet these responses are generally inadequate in eradicating the bacterium. Experiments in various animal models have established that immunization via the orogastric route can induce protective mucosal immune responses against gastric Helicobacter infections. Moreover, it was shown that active immunization could be used to eradicate an existent infection. Recently, several defined Helicobacter antigens were validated to be effective mucosal immunogens. One of these antigens (urease) has reached the clinical trial phase. Research toward the development of an H. pylori subunit vaccine has revealed that the stomach is a bona fide component of the common mucosal immune system.