The evidence in support of the dominant role of Helicobacter pylori in association with peptic ulcer disease (PUD) is reviewed. The epidemiology of PUD is in flux, however, and, in the future, H. pylori may become a less prevalent factor, because it now is in bleeding versus uncomplicated ulcers. Unfortunately, the accuracy of some diagnostic tests in bleeding ulcers may be lower than in uncomplicated ulcers. Concepts related to H. pylori virulence factors in ulcer disease, the pathophysiology of H. pylori ulcer disease, the interrelationships among H. pylori, NSAIDS, and ulcers, and the management of H. pylori ulcers are reviewed.