Now that the Food and Drug Administration is examining various treatment regimens for eradication of Helicobacter pylori (H. pylori) infection, the question of whom to treat has come to the forefront. Widespread attempts to eradicate the bacterium are not without risk, including the possibility of accelerating the emergence of resistant strains of the organism, in addition to possible adverse events of agents used to cure the infection. These risks are of concern to the Agency in the process of granting marketing approvals for various therapies. The association of H. pylori and duodenal ulcer (DU) is no longer disputed; however, data to date have been generated in studies of patients with active (acute) DU. In these patients, the benefits of eradication therapy are clear. Patients with a documented history of DU who do not have an ulcer crater at the time of presentation have not been well studied in controlled trials. If they are at similar risk for recurrence and complications, it follows that they, too, should be candidates for H. pylori testing and treatment. However, if, as some believe, duodenal ulcer disease becomes "inactive" or "burns out" with time, an argument could be made for expectant treatment for this subgroup of patients. The present review examines the available literature on the natural history of DU disease and explores the validity of the hypothesis of duodenal ulcer "burn out." Analysis of the data shows that there is little support for the phenomenon of duodenal ulcer disease "burn out," and that, in fact, DU disease resulting from H. pylori infection is a chronic, relapsing condition, lasting for decades, if not a lifetime. The literature is compatible with the view that, in the majority of patients, DU occurs on a background of an "ulcer diathesis" that is fueled by H. pylori infection, and "burns on, not out", until and unless the infection is extinguished. The true incidence of ulcer relapse is difficult to predict due to the common occurrence of asymptomatic ulcers and the poor correlation of symptoms with the presence of ulcer. Therefore, treatment of patients with a history of duodenal ulcer disease should be advocated, even if their ulcer disease is not "active," because the risk of recurrence and complications does not diminish unless the H. pylori bacterium is eradicated.