Even before the discovery of Helicobacter pylori as their cause, chronic gastritis and peptic ulcer disease were empirically treated with anti-infectious agents. However, it was not until that finding that an antibiotic approach began to be used systematically. The main aim of this article is to review the evolution of H. pylori therapy from a meta-analytical perspective. Initially, antibiotic monotherapy had a minor efficacy on H. pylori. Dual therapy including either bismuth compounds or proton-pump inhibitors (PPI) and one antibiotic also resulted in insufficient cure rates. Bismuth-based triple therapy (the first used) and PPI-based triple therapies (combined with two antibiotics, including amoxicillin, nitroimidazole, or clarithromycin) have been the most widely recommended. PPI-based regimens are superior to H2-antagonist-based ones. The influence of the type of PPI, the dose and the duration of the treatment will be discussed. Among the factors influencing the efficacy of therapy, resistance to clarithromycin and metronidazole are the most important risk factors for eradication failure. Several rescue therapies can be used. Bismuth-based quadruple therapy is effective, but the complexity of the regimen and the associated adverse effects limit the compliance. PPI-based triple therapy with amoxicillin and levofloxacin is at least equally effective and better tolerated.