In spite of confirmed evidence of clinical importance of H. pylyori infection in the etiopathogenesis of peptic ulcers it still remains a polyetiologic syndrome and in the therapy of peptic ulcers not only skill in standard methods but also „medical arts“ are needed. Apart from H. pylori presence in etiopathogenesis of peptic ulcers also further factors disturbing gastric acid secretion and protective function of endogastric and duodenal mucosa are considered. Most of these disorders are genetically predisposed but also excessive stress, dietary and regime habits and use of various unhealthy substances play a role. More frequent ulcerogenetic drugs abuse is reported. Lesions similar to peptic ulcers can be induced by the range of diseases that have to be considered and carefully diagnosed. These diseses are usually „resistant“ to standard therapeutic methods. On basis of experience of diagnosis and therapy of more than 1 , 700 patients with resistant ulcers the authors described diagnostic and differential diagnostic methods.