Helicobacter pylori induces chronic superficial gastritis which in some patients may lead to peptic ulcer disease, while a subset of infected individuals develop gastric cancer or gastric lymphoma. Consensus guidelines recommend that patients with a known H. pylori infection receive eradication treatment. Successful treatment requires that antibiotics be used in combination with acid suppressants or bismuth, and although the list of effective antibacterials is short, regimens such as amoxicillin and clarithromycin or metronidazole and clarithromycin with the proton pump inhibitor omeprazole have achieved eradication rates of approximately 90% in trials. However lower eradication rates are probably more common, and strains resistant to clarithromycin or metronidazole, or both, are of concern. Stable amoxycillin resistance has also been reported. Efforts are underway to discover and develop novel therapeutics, both H. pylori specific antibacterial drugs and a therapeutic vaccine. Impetus to these efforts has been provided by the availability of the genome sequences of two different H. pylori isolates. In the case of drug discovery, a genome-based strategy facilitates the expeditious selection of novel lethal targets not used by today's antibiotics, providing the opportunity to identify novel classes of antibacterials. Vaccine discovery and development has largely focused on a small number of antigens selected by conventional means. Recent reports that mucosal and serum antibody titers do not appear to be essential for protection against H. pylori in murine models suggest that that a wider range of H. pylori proteins than those previously considered may be able to induce protective immunity. Progress towards development of new H. pylori therapeutics is discussed.