The discovery of Helicobacter pylori has already changed the natural history of peptic ulcer disease, with most patients being cured at their first presentation. Similarly, the incidence of gastric cancer and other diseases related to H. pylori are likely to be greatly reduced in the near future. Isolation of the spiral intragastric bacterium H. pylori totally reversed the false dogma that the stomach was sterile, and it taught us that chronic infectious disease can still exist in modern society. Helicobacter pylori’s unique location, persistence, and evasion of the immune system offer important insights into the pathophysiology of the gut. Also, the fact that it was overlooked for so long encourages us to think “outside the box” when investigating other diseases with obscure etiologies. We should consider such provocative scientific ideas as bridges to the future disease control.