Despite the remarkable advances made in primary prevention and treatment, ischemic heart disease (IHD) remains the leading cause of death and a significant cause of disability in developed countries. Since traditional cardiovascular risk factors failed to predict all cases of IHD, there is an intensive research to explore other potential etiologic factors. Among these, numerous studies have considered the theoretical link between IHD and chronic infections, including Helicobacter pylori (H. pylori). Considering that epidemiologic studies have produced conflicting results, due to geographical variations of IHD and H. pylori prevalence as well as heterogeneity of study designs, an alternative way to analyze this topic is to assess if consistency for a biological plausibility exists. In this review we critically analyzed the experimental data on this topic, to assess whether their results could lead future clinical studies.