Despite improved understanding of peptic ulcer disease (PUD) pathogenesis, advances in diagnostic modalities, and the availability of modern pharmalogical, endoscopic and surgical treatments, gastroduodenal ulcer remains a major cause of morbidity and mortality worldwide. The predominant risk factors of this disorder remain Helicobacter pylori and ulcerogenic drugs. However, the proportion of idiopathic PUD is increasing worldwide often coinciding with the declining prevalence of H pylori infection. PUD heterogeneity worldwide is due to host genetic, bacterial and environmental factors. Variable ages in the acquisition of H pylori may influence the distribution of gastric versus duodenal ulcers as has the increasing use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Pharmacogenetics affects the magnitude of PUD risk induced by ulcerogenic drugs such as NSAIDs and also efficacy of proton pump inhibitors. Parietal cell mass and maximal acid output is higher in Western populations but it remains uncertain whether susceptibility to drug-induced PUD is influenced by race. H pylori antibiotic resistance also varies throughout the world. This review summarizes the similarities and differences in PUD aetiology, clinical features and treatment between the East and the West. In particular, we focus on the recent publications on the prevalence of H pylori, which is declining rapidly in various parts of the world resulting in overlapping prevalence rates in the East and the West.