Studies have demonstrated the superior efficacy of adding adefovir dipivoxil to existing lamivudine therapy compared with switching to adefovir dipivoxil monotherapy in patients with lamivudine-resistant chronic HBV infection. This Practice Point commentary discusses a study by Yatsuji et al., which investigated the long-term efficacy of adding adefovir dipivoxil to lamivudine as salvage therapy in a cohort of 132 patients with lamivudine-resistant chronic HBV infection. After 2 years of treatment, approximately 80% of patients achieved HBV DNA levels less than 400 copies/ml, and only 1.6% of patients developed adefovir-dipivoxil-resistant viral mutations during follow-up. Although these results are promising, the duration of follow-up in this study is too short to draw a definitive conclusion concerning the efficacy of this so-called adefovir dipivoxil 'add-on' strategy, as resistance rates could rapidly increase over time. In addition, tenofovir disoproxil seems to be superior to adefovir dipivoxil in this setting and treatment strategies focused on the prevention of drug resistance should be investigated.