Gastric cancer is the second commonest cause of cancer-associated death in the world. The high mortality is largely attributed to the huge number of at-risk individuals as well as the delay in presentation. Hence, chemoprevention of gastric cancer appears to be the most promising approach in reducing the incidence and mortality related to this cancer. Among various chemoprevention strategies, Helicobacter pylori eradication is the one being most extensively examined. Results from several large-scale prospective randomized studies, however, showed marginal benefits of H. pylori eradication on regression of premalignant gastric lesions. Moreover, there is no significant reduction in gastric cancer incidence. Similarly, ascorbic acid and/or beta-carotene supplementation have borderline effects on premalignant gastric lesions. Based on epidemiological data, the use of non-steroidal anti-inflammatory drugs is associated with a reduced risk of stomach cancer. Future studies should evaluate the role of other chemopreventive agents, particularly specific cyclooxygenase-2 inhibitors, in reducing the risk of gastric cancer.