Gastric adenocarcinoma is the second leading cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the strongest recognized risk factor for gastric adenocarcinoma. This bacterial species colonizes the stomach of more than half of the world's population; however, only a very small proportion of infected subjects develop adenocarcinoma. H. pylori causes a chronic gastritis that may last decades, and a multistep precancerous process is recognized for the most frequent histologic type of gastric adenocarcinoma: the intestinal type. The severity and long-term outcome of this infection is modulated by an increasing list of bacterial, host, and environmental factors, which interplay in a complex manner. Identification of individuals at high risk for gastric cancer that may enter a surveillance program and intervention during the precancerous process is the most suitable strategy for decreasing mortality due to this malignancy.