One hundred years ago, the role of the vagal nerve in gastric acid production was established. After the second World War, this paradigm served as the basis of treatment of peptic ulcer disease by pharmacological or surgical means. A remarkable parallelism between the developments of both approaches was observed in the 1970s. On the one hand, medication with less side effects became available. On the other hand, vagotomies were becoming more physiologic in nature and produced less postoperative symptoms. The elusive nature of peptic ulcer disease and the inability to cure this by medication were acknowledged. Very few investigators, however, had reported on a possible infectious origin of peptic ulcer disease and those reports were old. After 1984, the role of Helicobacter pylori in the disease was discovered. With this shift in paradigm, the treatment of peptic ulcer disease changed radically, despite attempts in the surgical community to develop simplified operations. This illustrates that neither the most powerful acid reducing drugs on their own, nor the most physiological and least invasive surgical techniques stand the test of time if the underlying paradigm changes. It also illustrates that old ideas should not be overlooked.