Helicobacter pylori infect during childhood and are typically present for life, despite a vigorous host immune response, which includes the invading pathogen being coated with antibodies. This bacterial longevity indicates the development, on the part of the pathogen, of a range of processes for evading effective host immunity. Since its discovery 25 years ago, significant progress has been made in understanding the virulence factors and several aspects of the pathogenesis of H. pylori gastric diseases. The prevalence of antimicrobial drug resistance is so high that all patients infected with H. pylori should be considered resistant infections. The most severe consequence of H. pylori infection, and the key reason a vaccine is required, is gastric cancer, globally the third leading cause of death due to cancer. Patients typically present with gastric cancer without knowing they are infected; eradication likely has little effect by this time. Vaccine against H. pylori that reduces the incidence of gastric cancer will probably be cost effective in developed countries. Several vaccines were successfully tested in different experimental animal models, but translation into an efficacious human vaccine has been unsuccessful.