Infection with the gastric bacterium Helicobacter pylori invariably leads to active chronic gastritis, and is strongly correlated to peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. The infection leads to local accumulation of inflammatory cells and strong activation of B- and T-cell immunity. Still, the immune response can not eliminate the bacteria, and unless antibiotic treatment is used, the infection is usually lifelong. During the last few years, several immunomodulatory properties of H. pylori have been described, which probably contribute to the inability of the immune system to eradicate the bacterium. Another factor promoting bacterial persistence is probably the induction of a substantial regulatory T-cell response by the infection. Several different immunization schedules have resulted in protective immunity in animal models, while in humans no reliable vaccine is available as yet. In this article, we describe the innate and adaptive immune responses to H. pylori, and the attempts to create an effective vaccine.