Gastric cancer is the second most common cause of cancer death in the world. Helicobacter pylori infection is now a well-accepted cause of this malignancy; in some parts of the world, up to eighty percent of all gastric cancers are at least in part caused by H. pylori infection. H. pylori infection typically starts in childhood as an inflammatory process in the stomach. The changes in the gastric microenvironment facilitate gastric cancer over time. Among infected individuals, genotype of H. pylori, coincident environmental exposures, and genetic factors of host seem to play roles in determining who will get gastric cancer and who will not. Unfortunately, it remains unknown whether treatment of H. pylori prevents gastric cancer. Thus, screening for H. pylori to prevent cancer is not yet widely recommended. Some consensus groups, however, have recommended screening for and treating H. pylori infection in individuals with family histories of gastric malignancy. In high-risk countries, screening programs for early gastric cancer itself may improve therapeutic outcome for this highly lethal disease.