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Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer. The efficacy of 1 week triple therapies, which often have eradication rates of > 90%, is undermined by poor patient compliance and bacterial antimicrobial resistance. The development of new anti-H. pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H. pylori. Animal models of H. pylori infection have been developed but their clinical validity has yet to be established. Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging.