Recommendation for the diagnosis and treatment of Helicobacter pylori Infection are defined in recent national and international guidelines. In Germany, proton pump inhibitor-based triple therapy with clarithromycin and metronidazole or amoxicillin is still the standard in first line therapy. However, success rates have decreased substantially during the last years due to increasing antibiotic resistance, particularly in patients from Southern Europe. In addition, antimicrobial resistance rates against the standard antibiotics further increases dramatically after failure of first line therapy deeming the repeated use of these antibiotics basically impossible. Against this background, a critical appraisal and eventually adaption of therapeutic options both in first line and rescue treatment appears necessary. This paper gives an overview on the current status of therapeutic options and developments in the treatment of H. pylori infection in the light of increasing antibiotic resistance.