Helicobacter pylori infection is now recognized as the major cause of chronic gastritis throughout the world. A fraction of infected persons develop peptic ulcer disease or gastric cancer, accounting for its clinical significance. The pathophysiology of this infection can be better understood by considering five central concepts-heterogeneity of strains, persistence of infection, immunological down-regulation, physiological consequences and variability in outcome. Microbial, host and environmental factors must each contribute to the outcome variation.