Helicobacter pylori causes persistent inflammation in the human stomach, yet only a minority of persons harbouring this organism develop peptic ulcer disease or gastric malignancy. An important question is why such variation exists among colonized individuals. Recent evidence has demonstrated that H. pylori isolates possess substantial phenotypic and genotypic diversity, which may engender differential host inflammatory responses that influence clinical outcome. For example, H. pylori strains that possess the cag pathogenicity island induce more severe gastritis and augment the risk for developing peptic ulcer disease and distal gastric cancer. An alternative, but not exclusive, hypothesis is that enhanced inflammation and injury is a consequence of an inappropriate host immune response to the chronic presence of H. pylori within the gastric niche. Investigations that precisely delineate the mechanisms responsible for induction of gastritis will ultimately help to define which H. pylori-colonized persons bear the highest risk for subsequent development of clinical disease, and thus, enable physicians to focus eradication therapy.