Peptic ulcer disease – chiefly gastric and duodenal ulcers – remains of global importance to human health. The majority of peptic ulcers are caused by Helicobacter pylori (Hp) infection or nonsteroidal anti‐inflammatory drug (NSAID) use, including aspirin. However non‐Hp, non‐NSAID ulcers are becoming more common. Healthcare practitioners from different countries face different diagnostic and therapeutic challenges, at both the patient and population level. These arise from the changing epidemiology of the major causes, differences in Hp antibiotic resistance, and other temporal and geographical trends. Fundamental considerations in management are however constant: firstly treatment to achieve ulcer healing; and secondly the identification and management of specific causes – particularly eradication therapy for Hp and preventative strategies for drug‐induced ulcers.