In this review we evaluate the pros and cons of Helicobacter pylori invasion of epithelial cells as part of the natural history of H. pylori infection. H. pylori is generally considered an extracellular microorganism. However, a growing body of evidence supports the controversial hypothesis that at least a subset of H. pylori microorganisms has an intracellular (intraepithelial) location. Most significant is the fact that H. pylori invades cultured epithelial cells with invasion frequencies similar to Yersinia enterocolitica and better than Shigella flexneri; furthermore, studies of invasion mechanisms suggest that H. pylori invasion of and survival within epithelial cells is not merely a passive event, but requires active participation of the microorganism. Although many studies of human gastric biopsy specimens have failed to demonstrate any intracellular H. pylori, some studies have revealed a minor fraction of H. pylori inside gastric epithelial cells, with possible linkage to peptic ulceration and epithelial cell damage. In conclusion, these data encourage further research to establish whether intracellular H. pylori does play a role in H. pylori colonization of the human stomach and in peptic ulcer pathogenesis.