The approvals and provisions of the Management of Helicobacter pylori infection-the Maastricht V/ Florence Consensus Report and those of the Kyoto Global Consensus Conference on H. pylori-associated gastritis, concerning with the primary and secondary prevention of gastric cancer (GC), unambiguously suggest that H. pylori infection is the most important risk factor of GC. Accordingly, the basis for the primary and secondary prevention of GC is the optimization of H. pylori eradication therapy. The clear direct relationship of the risk of GC to the severity and extent of atrophic gastritis, intestinal metaplasia and dysplasia and no reversal of intestinal metaplasia and dysplasia in the presence of H. pylori eradication presume that gastroprotective agents should be used for primary and secondary prevention. Experimental and clinical findings can lead to the conclusion that rebamipide is a highly effective and safe agent for the primary and secondary prevention of GC in patients with and without H. pylori infection, by optimizing anti-Helicobacter therapy, its anti-inflammatory effect and ability to restore the cellular structure of the gastric epithelium.