Although much is known about the virulence of Helicobacter pylori, the transmission pathways for this bacterium are still unresolved. Transmission has been addressed through: (1) prevalence within families; (2) detection in fecal/oral environments; (3) detection in the abiotic/biotic environment; and (4) direct inference from strain similarity. Here, we review the molecular and biochemical methods used and discuss the relative merits of each. Furthermore, as there are differences between developing and developed nations, we discuss the results obtained from transmission studies in light of the study population. We conclude that H. pylori is probably transmitted person-to-person, facilitated by fecal–oral transmission during episodes of diarrhea or gastro-oral contact during periods of vomiting. The persistence of H. pylori in abiotic and biotic environments remains unproven but possible reactivation from viable, non-culturable coccoid forms should be further investigated. Finally, we speculate on the effect of host–pathogen interactions in confounding the inference of transmission.