The treatment of Helicobacter pylori infection is jeopardized by resistance to the antibiotics used, which turns out to be the main risk factor for failure. Resistance is due to point mutations. For clarithromycin only two sites in the 23S rRNA sequence are concerned and can be easily detected by molecular methods, while for metronidazole several mutations on rdxA and other genes can be responsible and so do not allow such detection. The situation for the rare cases of amoxicillin resistance is not fully determined. The impact of resistance on the clinical outcome is dramatic for clarithromycin while it only decreases the success by 20% for metronidazole.