Triple therapy with clarithromycin and proton-pump inhibitors (PPI) is the recommended regimen for Helicobacter pylori eradication in Europe, the USA, and Canada. This treatment was first described by Italian researchers and has been the mainstay of therapy against H pylori for more than a decade. Eradication rates of over 90% were initially reported and in clinical practice these regimens consistently achieved success rates of over 80%. The efficacy of 7-day triple therapy has been decreasing, however, and now falls below the 80% recommended by guidelines. The reason for this decrease could relate to the increasing use of eradication regimens in functional dyspepsia, less pathogenic strains of H pylori, or an increasing incidence of macrolide resistance.