Infection with Helicobacter pylori, is one of the most prevalent infections world-wide, where approximately 50% of adults in the developed world and over 90% of inhabitants in the developing world are infected. Chronic infection with H. pylori is the cause of gastritis, peptic ulcer disease and is a risk factor for gastric adenocarcinoma. Recent studies have demonstrated the suitability of an immunization strategy in the prevention and treatment of H. pylori infection, and the potential for management of disease. Mucosal administration of purified recombinant sub-unit proteins of H. pylori, together with a mucosal adjuvant, has identified urease to be highly efficacious in prophylactic and therapeutic animal model studies, and show partial therapeutic activity in humans. Several other antigens are also effective, and the recent sequencing of the H. pylori genome has led to an intensive effort in antigen discovery. Other research has centered on the identification of novel approaches for delivery, and the immunological mechanisms underlying protective immunity. In this review, preclinical data and the results of early-stage clinical trials and directions for future research on Helicobacter vaccines are described.