Helicobacter pylori resistance to antibiotics is increasingly reported and may limit the efficacy of current treatment regimens. Their resistance mechanism has been found to be point mutations for all antibiotics. Macrolide resistance is the most clinically important, but can be detected efficiently by molecular methods. Metronidazole resistance has limited clinical impact but testing methods are not reliable. Seldomly found cases of resistance, such as to amoxicillin and tetracycline, have had their mechanism recently elucidated. The existence of rapid and practical methods for the detection of macrolide resistance (eg, Fluorescence Resonance Energy Transfer assay) should improve management of H pylori-positive patients in the future, by allowing an adapted first-line therapy.