INTRODUCTION: Helicobacter pylori is a Gram-negative bacterium that causes chronic gastritis, dyspepsia, peptic ulcers, and gastric cancer. Over half the world's population is infected with H. pylori, with higher prevalence in developing countries. Areas covered: In this review, current guidelines on H. pylori therapy, such as the Toronto consensus statement, the Maastricht V/Florence consensus report, and the American College of Gastroenterology guidelines, are compared. Also, we analyzed reports of antimicrobial resistance of H. pylori published in PubMed in the last years to determine current antimicrobial resistance worldwide. Expert commentary: Although H. pylori antimicrobial resistance varies by geographic area, its prevalence has been increasing over time, causing therapy failures and low eradication rates. To best optimize the management of H. pylori infection, H. pylori therapy should be based on patterns of local and individual antimicrobial resistance, if possible.