Despite advances in surgical treatment and chemotherapy, gastric cancer remains a major global health burden. The most recent estimates show that it is the fourth most common cancer and the second most common cause of cancer deaths worldwide. Various etiologic factors have been linked with the disease. It is widely accepted that Helicobacter pylori infection and high salt intake are positively associated with this neoplastic process. Controversial associations have been found with smoking or drinking habits. In contrast, there is convincing evidence that the adequate consumption of fresh fruits and vegetables reduces the risk of gastric cancer. Prevention intervention trials involving antioxidant supplements and anti- H. pylori treatment have shown beneficial effects in preventing the progression of pathologic changes in the gastric mucosa. On the other hand, recent advances related to differences in the genotypes of the bacteria and in human cytokine polymorphisms would allow the design and implementation of large-scale screening programs to identify subjects at the highest risk of gastric cancer. Curing the infection in such subjects and supplying adequate amounts of antioxidants should prevent a neoplastic outcome, and this intervention should be monitored by endoscopic surveillance.