Acquired resistance of Helicobacter pylori to metronidazole and clarithromycin has been reported, with metronidazole resistance being very common. This has an important clinical impact on dual therapies, as well as on the standard triple therapies. However, when antisecretory drug based triple therapies with amoxycillin or clarithromycin and metronidazole are used, the resistance can be overcome in up to 75% of the cases in most of the studies. Clarithromycin seems to be a better choice than amoxycillin to achieve this goal. Nevertheless, resistance to metronidazole remains a risk factor for treatment failure. The most precise information comes from studies in which minimum inhibitory concentrations (MICs) are reported as well as whether the strain is susceptible or resistant. Few data are available from clinical trials to measure the impact of clarithromycin resistance. However, such resistance seems to have a negative impact on the clinical outcome of treatment. It is of greater importance that H pylori resistance is closely monitored in the future.