Intensive investigation into the interactions of Helicobacter pylori with the human host during the period of this review has led to several important developments in our understanding of H. pylori pathogenesis. There is direct evidence to support a central role for bacterial adhesion to host gastric epithelial Lewis antigens. Adherence can result in activation of host signaling cascades, including tyrosine phosphorylation events. H. pylori induces an immune response that is skewed toward a T-helper cell (Th) 1 phenotype, and an insufficient Th2 response is associated with the inability of the host to eradicate the organism. An area of active investigation has been the induction of epithelial apoptosis, both in direct response to H. pylori and by T-cell mediated pathways. Although the consensus is that the cagA gene product is not involved in pathogenesis, the presence of the cag pathogenicity island is associated with increased gastric inflammation and decreased epithelial repair. Interestingly, infection with cagA+H. pylori appears to result in decreased prevalence of both gastroesophageal reflux disease and adenocarcinoma of the esophagus and cardia.