The discovery of Helicobacter pylori has greatly changed our approach to peptic ulcer disease. Bacterial, host, and environmental factors all have a role in peptic-ulcer disease. Although the prevalence of uncomplicated peptic ulcers is falling, hospital admissions for ulcer complications associated with non-steroidal anti-inflammatory drugs (NSAIDs) are rising. Evidence suggests that prescription of NSAIDs along with potent antiulcer agents and the use of highly selective cyclo-oxygenase-2 inhibitors reduce gastroduodenal ulceration. Whether these therapeutic advances will translate into clinical benefits remains to be seen. The interaction between H pylori and NSAIDs is one of the most controversial issues in peptic ulcer disease. With the fall in rates of H pylori infection, the proportion of ulcers not related to this organism and NSAIDs has risen, which will affect the management of peptic ulcer.