Helicobacter pylori induces persistent inflammation in the human stomach, yet only a minority of colonized persons develop peptic ulcer disease or gastric malignancy. Numerous studies published in the last year have demonstrated that H. pylori isolates possess substantial phenotypic and genotypic diversity, which may engender differential host inflammatory responses that influence clinical outcome. Results from these recent investigations have more precisely delineated the mechanisms of H. pylori pathogenesis, which will ultimately help to define colonized persons bearing the highest risk for disease, and enable physicians to appropriately focus diagnostic testing and eradication therapy.