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Helicobacter pylori is an important human pathogen, responsible for most peptic ulcer disease, gastritis and gastric malignancies. H. pylori has several unique features: it is highly adapted for gastric colonization, yet it produces clinical consequences in a small minority, its genome is known, and it is the only bacterium strongly associated with cancer. H. pylori is therefore of great interest to clinicians and researchers of many, often disparate, disciplines. We highlight recent advances in this fast changing field from many different areas.The major contentious clinical issues relate to the synergistic gastrotoxic interactions of H. pylori with non-steroidal anti-inflammatory drugs, and a possible association of H. pylori with atherosclerotic events. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. Studies of pathogenesis have been aided by increasingly sophisticated murine models. The effects in gastric epithelial cells of two of the major virulence factors (genes within the cag pathogenicity island and the vacuolating cytotoxin, VacA) of H. pylori illustrate the complex network of cellular reactions activated by H. pylori. The metabolism of H. pylori is dependent on the availability of hydrogen.Basic science research into H. pylori continues to elucidate the mechanisms by which H. pylori infection causes disease. These findings have implications for the design of novel therapies and for improving clinical strategies to identify at-risk individuals. Many are also worthy of consideration for other epithelial-microbial interactions.