Helicobacter pylori is one of the most common bacteria worldwide. It infects more than 50% of the human population, and causes serious gastric diseases, such as chronic gastritis, peptic ulcer and, in some individuals, gastric cancer. The current treatment with antibiotics is not without drawbacks. The development of vaccines could help enormously in reducing the burden of H. pylori-associated diseases. A large body of evidence from experimental animal models has shown that vaccine-mediated prevention or vaccine-induced eradication of H. pylori is feasible. Several issues, however, are still unresolved, concerning the quality of the induced immune response necessary to achieve strong and sustained protective immunity in man. Several trials in humans are planned for the next few years. These studies will tell whether vaccination against H. pylori is feasible in man, and will offer the great opportunity to understand better the relationship between this ancient bacterium and humans.