The decline in gastric cancer mortality is a major achievement in cancer control. It has been attributed to a set of factors related to the improvement of the populations’ living conditions, namely the increase in the consumption of fruit and vegetables and the decrease in salt intake, and therefore labelled as an ‘unplanned triumph’. In the last decades, however, we witnessed the gradual acceptance of Helicobacter pylori infection as the most important environmental factor contributing to the occurrence of gastric cancer. The potential for further reducing the burden of cancer by acting on a single modifiable exposure, that is, preventing or treating infection, and the extent to which it may be achieved, requires an in-depth knowledge of the contribution of H. pylori infection to the causal mechanisms leading to cancer. We propose a conceptual framework for the interpretation of the role of H. pylori infection in the web of gastric cancer causation, taking into account the nosological heterogeneity of gastric cancer, the induction period for the action of H. pylori infection and its potential role as a necessary component cause.