Peptic ulcer disease is a chronic, relapsing disease. Successful healing of duodenal and gastric ulcers with antacids, cimetidine, ranitidine, famotidine, or sucralfate is frequently followed by ulcer recurrence. The need for long-term, low-dose maintenance therapy is based on disease severity, ulcer history, complications, therapeutic intervention, response to treatment, and potential risk factors. Comparison of ulcer maintenance trials requires consideration of important factors such as frequency of endoscopy, duration of follow-up period, and the method used to calculate ulcer recurrence rates. Clinical trials indicate that chronic treatment with low-dose cimetidine, ranitidine, famotidine, and probably sucralfate decreases the frequency of duodenal ulcer recurrence and that ranitidine may be superior to cimetidine. Preliminary studies indicate that higher doses of these same medications may be required to prevent gastric ulcer recurrence. Long-term maintenance therapy with these agents must be continuous in order to prevent relapses, but treatment should be limited to one year because of unknown consequences beyond this period.