In animals, oral immunization can prevent or cure Helicobacter pylori infection, and prevent reinfection. Several antigens of the pathogen have been identified as protective antigens, and some appear to be well suited for use in an human vaccine. Initial clinical studies have shown that urease is safe in humans, and immunogenic in Helicobacter pylori-infected volunteers. The design of a protective vaccine in humans will probably depend upon the combination of two or more antigens, the identification of the optimal route of immunization, and the use of appropriate vaccine delivery systems. Because a vaccine against Helicobacter pylori is likely to be effective regardless of the mode of transmission of the infection, it represents a potential alternative to current therapies, with the added advantage of having a direct impact on the reservoir of the infection.