INTRODUCTION: The nucleotide analogue adefovir dipivoxil (ADV) was approved in 2002 for the treatment of chronic infection with hepatitis B virus (HBV), in both hepatitis B e antigen (HBeAg)-positive and -negative patients. ADV 10 mg daily has been associated with improved liver histology, decreased levels of HBV DNA and alanine aminotransferase (ALT), and seroconversion of HBeAg. AREAS COVERED: This paper reviews the use of ADV as a first-line treatment for chronic hepatitis B and as an add-on therapy in chronic HBV-infected patients with lamivudine resistance. In the years since its launch, clinical resistance to ADV has emerged, and tenofovir and entecavir have shown greater efficacy in reducing viral load. EXPERT OPINION: Many patients who started antiviral therapy with ADV (either as monotherapy or in combination with lamivudine) remain on this agent because they have undetectable viremia, but its future use will probably diminish because of the availability of more potent drugs. ADV is generally well tolerated, though the 10 mg dose is associated with low risk of nephrotoxicity.