Helicobacter pylori plays an important role in the pathogenesis of chronic active gastritis, peptic ulcer and gastric mucosa-associated lymphoid tissue-lymphoma, and is also involved in carcinogenesis of the stomach. Since now no current first-line therapy is able to cure the infection in all treated patients. We evaluated data on the most successful therapy regimens—sequential, concomitant and quadruple therapies—and on the standard therapy available for H. pylori eradication. When therapy fails several factors may be involved: we reviewed both bacterial and host factors that can affect the eradication and that can be involved in therapeutic management of the H. pylori infection.