Today, the lifetime prevalence of peptic ulcer disease is in industrialized countries approximately 5 to 10%. There has been a substantial decline in peptic ulcer incidence and mortality over the last forty years. The two principal, independent risk factors of gastric and duodenal ulcer disease are a preexisting Helicobacter pylori infection and the regular intake of nonsteroidal anti-inflammatory drugs (NSAID). Several characteristics of H. pylori infection which contribute to the final event of ulceration have been identified. Bacterial virulence factors and the severity of gastritis seem to play an important role. It remains unclear, whether the degree of gastritis is due to host factors or to the pathogen. NSAID-induced peptic ulcers are often asymptomatic and therefore diagnosis is not being made until complications arise. NSAID-ulcers often bleed. NSAID ulceration can induced develop already after a short course of treatment. The combination of NSAIDs with anticoagulants or corticosteroids potentiates the ulcer risk. Age, diet, smoking and psychological factors have a rather permissive and optional influence on peptic ulcer pathogenesis.