Although H. pylori infection is endemic and despite more than 10 years of research, the mode and route of transmission remain elusive. This may, in part, be due to the inherent problems of detecting H. pylori noninvasively. The prevalence of infection varies between countries and is closely related to Growth Domestic Product. An age-cohort effect and data from longitudinal studies suggest that the incidence of infection is much higher in children than adults. In developing countries the prevalence of infection is often more than 80% in young adults, in contrast to less than 10% for similar age groups in developed countries. The observations of mosaicism (in the VacA gene) and a panmycytic population structure imply exchange of genetic material either in or outside of the host, which is supported by the increasing recognition of polyclonal infection and suggests that secondary infection occurs after primary acquisition. In addition, in children persistent primary infection may sometimes occur only after previous (repeated) exposure and/or transient colonisation of the gastric mucosa. H. pylori and other gastric Helicobacter spp are always noninvasive, but other human nongastric Helicobacter spp have sometimes been isolated from the systemic circulation in immunocompromised patients. For nonhuman hosts, intestinal Helicobacter spp are thought to translocate more frequently from the colon to the liver. Within the human host, the oral cavity is the principal extragastric reservoir, although case reports suggest that H. pylori may sometimes be found beyond the 2nd part of the duodenum. The hypothesis that H. pylori is a zoonosis or transmitted as coccoid forms by a vector (pets, houseflies) is not supported by recent research showing that H. pylori is entirely unable to support an aerobic or anaerobic metabolism and that coccoid forms are non-viable. H. pylori is primarily acquired in infancy, most probably via the oroorogastric route, from other family members or close contacts encountered after weaning or socialisation. Further studies to support or refute this hypothesis are required.