Helicobacter pylori infects the stomach of > 50% of the human population worldwide, with higher prevalence in the developing countries. A strict correlation between H. pylori infection and gastroduodenal diseases has been demonstrated, including gastritis, peptic ulcer and gastric cancer. Current therapies against H. pylori consist of an antisecretory plus antibiotics. These therapies are effective in 80 - 90% of the cases; presently, no alternative therapies have been shown to give comparable or better results. There are two main reasons for therapy failure: poor compliance, which results in cure discontinuation, and antibiotic resistance. To overcome the drawbacks inherent to any antibiotic therapy, a prophylactic vaccine seems to be the most reasonable approach. Vaccines have been developed based on data obtained in animal models, a number of which are currently in Phase I clinical trials, in some cases giving encouraging data for safety and immunogenicity. In the absence of any immunological correlate of protection against H. pylori, it will be possible to evaluate the efficacy of these vaccines only in large Phase III clinical trials.