Classical risk factors explain the pathogenesis of coronary heart disease (CHD) in only a proportion of cases; therefore, the need to investigate the possible role of "new" agents has incited intense research. Since 1994, a number of studies regarding the possible involvement of Helicobacter pylori (H. pylori) have been published with conflicting results. Establishing a causal link between this infection and CHD would be of major public health importance, since the eradication of the bacterium is easy and much less expensive than long-term treatment of the other risk factors. The main cause of this discordance was the vast heterogeneity of such studies: sufficiently powerful design was found only in few investigations, CHD was defined with a low degree of homogeneity, biases were obvious in the control groups, thus giving room for large variation in the adjustment of potential confounding factors. The present paper attempts to highlight the future directions towards which research should be headed in this area to establish a causal role of H. pylori infection in the pathogenesis of CHD. Future research should take three directions: 1) prospective population-based studies in which the incidence or the recurrence of CHD be evaluated in correlation with H. pylori status, 2) intervention trials, focusing separately on the chronic and acute phases of coronary heart disease and, 3) studies of physiopathology (both in the animal model and humans) to understand the potential biological plausibility.