The safety profile of low-dose maintenance therapy with H2-antagonists for duodenal ulcer disease suggests that these agents can be given safely for several years and probably much longer. Because information regarding the use of these compounds for more than 10 years in large numbers of patients is lacking, the safety of these drugs should continue to be monitored. The safety profiles of famotidine and nizatidine will require several additional years of postmarking surveillance data to match the depth of our knowledge regarding cimetidine and ranitidine. Compared to a surgical approach to ulcer disease, continuous H2-blocker maintenance therapy is cost-effective and is associated with significantly less morbidity. Patients with a history of bleeding or other ulcer complication should be encouraged to remain on maintenance therapy if they do not undergo surgery. The need for extended maintenance therapy also applied to individuals with frequent symptomatic ulcer relapses, reflux oesophagitis, and a range of less common disorders. Currently, H2-blockers and sucralfate are the only agents approved by the Food and Drug Administration for maintenance therapy of duodenal ulcer disease. Experience with omeprazole is still limited, and its long-term safety profile must await the completion of controlled trials of maintenance therapy. Given the apparent long-term safety of the H2-blockers for maintenance therapy, any new agent must prove to be equally safe in the clinical arena, a task that may be indeed formidable.