Tenofovir disoproxil fumarate is a nucleotide analog reverse transcriptase inhibitor recently approved by the United States Food and Drug Administration (FDA) for the treatment of chronic hepatitis B virus (HBV) infection in adults. Tenofovir has been available in the United States for the treatment of human immunodeficiency virus (HIV) since 2001. It blocks HBV replication in liver cells and is available as a once-daily oral formulation. The efficacy of tenofovir for the treatment of chronic HBV has been demonstrated to be superior to adefovir in randomized controlled trials, which led to its FDA approval for use in chronic HBV. Because of its potent antiviral activity, favorable safety profile, and higher barrier to the development of resistance, tenofovir should replace adefovir as a first-line monotherapy option in the treatment of HBV in monoinfected patients. In the HIV-HBV-coinfected population, tenofovir is already a preferred agent in combination with other anti-HBV agents (lamivudine or emtricitabine), which are cotreatments for HIV as well. In addition, tenofovir monotherapy or in combination with nucleoside analogs are options for patients who have developed resistance to other therapies for chronic HBV, including lamivudine and adefovir.