Despite the decreasing frequency of Helicobacter pylori-induced peptic ulcers, peptic ulcer disease remains a major clinical problem partly because nonsteroidal anti-inflammatory drug ulcers have increased in frequency. The reduction in nonsteroidal anti-inflammatory drug ulcers by use of selective cyclooxygenase-2 inhibitors will not eliminate the problem because of increased use of aspirin for cardiovascular prophylaxis. This article reviews current concepts of peptic ulcer pathogenesis and therapy according to ulcer etiology; discusses potential interactions between etiologies; and considers the therapy for H pylori infection including the effects of antimicrobial resistance, and the role of bismuth quadruple therapy or furazolidone salvage therapy.