Resistance to antibiotics is considered as the primary reason for failure of eradication therapies. Resistance to clarithromycin is due to a decrease in binding to the ribosomes associated with a point mutation on the 23S rRNA. Its rate in Europe varies from 0-15%, with 5% in the UK. The resistance influences dramatically the success of the treatments. Resistance to metronidazole is due to a lack of reduction of this compound whose genetic basis is still unknown. The resistance rate in Europe varies from 10-50%, with 25% in the UK. It influences the success of treatments to a lesser extent than clarithromycin resistance. The initial eradication treatment can be prescribed without testing for susceptibility and must include a combination of two antibiotics, while stressing the importance of compliance to the patient. In case of failure, susceptibility testing must be performed. Few data are currently available on alternative therapeutic strategies when H. pylori is resistant to both clarithromycin and metronidazole.