The incidence of gastric cancer has decreased in much of the world, but gastric cancer remains the second leading cause of cancer death globally, and the burden is growing in many countries in East Asia and Latin America. Chronic infection with Helicobacter pylori is the dominant cause of gastric cancer, and two recent randomized trials showed that H. pylori eradication significantly decreased gastric cancer risk. Population screening and treating individuals for H. pylori also appears to be cost-effective. Nevertheless, current clinical guidelines differ as to whether asymptomatic adults should be screened and treated for H. pylori, and no countries have yet implemented eradication programs. Some of this inaction may reflect lingering doubts about the effectiveness of H. pylori eradication in preventing gastric cancer, but there is also uncertainty about possible risks of mass antibiotic treatment and its impact on gut flora. Appropriately designed studies will help address these issues and hasten the implementation of population-wide prevention programs.