The pathogenesis, incidence, complication rates, response to acid suppression and Helicobacter pylori (H. pylori) eradication therapy in peptic ulcer associated with chronic disease such as liver cirrhosis, chronic renal failure, diabetes mellitus, and critically ill conditions are different from those with general population, so that the management strategies also should be differentiated. The eradication of H. pylori are not so effective for preventing recurrence of peptic ulcer in liver cirrhosis patients as shown in general population, and conservative managements such as preventing deterioration of hepatic function and decrease in portal pressure are mandatory to reduce the risk of ulcer recurrence. The standard triple therapy for H. pylori eradication are as effective in chronic renal failure patients as in normal population, but the frequency of side effects of amoxicillin is higher in the patients not receiving dialysis therapy. Delay in eradication therapy until beginning of dialysis therapy or modification of eradication regimen should be considered in such cases. High prevalence of asymptomatic peptic ulcers and increased mortality in complicated peptic ulcer disease warrant regular endoscopic surveillance in diabetic patients, especially with angiopathy. The prolongation of duration of eradication therapy also should be considered in diabetic patients with angiopathic complication because of lower eradication rate with standard triple regimens as compared to normal population. Prophylactic acid suppressive therapy is highly recommended in critically ill patients with multiple risk factors. Herein, we propose evidence-based treatment guidelines for the management of peptic ulcer disease in special conditions based on literature review and experts opinion.