Helicobacter pylori is a Gram-negative bacterium that infects the stomach of more than half of the world's population. H. pylori infection is an established risk factor for gastric cancer, although it is not sufficient cause for the appearance of cancer, per se. Several studies have investigated the role of this bacterium in non-cancer diseases, including gastritis ulcer, duodenal ulcer, gastroesophageal reflux, cardiovascular diseases, neurodegenerative diseases, ocular diseases, and dermatological disorders. DNA damage and failure in antioxidant defences is a common denominator of many among these pathological conditions. The clinical outcome of H. pylori infection is dependent on many variables, including H. pylori genotype, host health status, host genotype, and host exposure to environmental factors. The role of genetic and environmental factors is reviewed in this paper. Among non-cancer diseases, idiopathic thrombocytopenic purpura appears to show the strongest link with H. pylori. There is an evidence for a role of CagA-positive H. pylori infection in atherosclerosis and ischemic heart disease. On the whole, the major factors playing a pathogenic role in H. pylori-related non-cancer diseases are: (a) host polymorphisms in genes involved in inflammation and protection against oxidative damage, (b) host exposure to dietary genotoxic agents, and (c) bacterial genetic polymorphisms. In conclusion, there is an evidence that mutagenesis-related mechanisms play a pathogenic role in the appearance of non-cancer diseases following H. pylori infection.