Peptic ulcers and gastric malignancies are the two major complication of the course of Helicobacter pylori-associated chronic gastritis. Both gastric adenocarcinomas and MALT lymphomas occur in association with H. pylori infection, and studies support an etiological association. This article discusses the natural history of H. pylori-related gastric carcinogenesis and criteria to identify people susceptible to H. pylori infection-associated gastric cancer. It then reviews the molecular and genetic mechanisms underlying the malignant transformation of the gastric mucosa associated with H. pylori.