More than 350 million individuals worldwide are chronically infected with hepatitis B virus (HBV). Individuals with chronic hepatitis B infection carry a significantly increased risk of life-threatening liver sequelae including cirrhosis, hepatic decompensation and hepatocellular carcinoma. Currently, antiviral therapy options for chronic HBV consist of immunomodulators, nucleoside analogues and nucleotide analogues. Tenofovir disoproxil fumarate, an oral prodrug of the phosphonate nucleotide tenofovir, was recently approved in 2008 for the treatment of chronic hepatitis B in the European Union and the United States. Tenofovir disoproxil fumarate is safe, well tolerated and has long plasma and intracellular half-lives, thus allowing for once-daily administration. Since its approval, tenofovir disoproxil fumarate has become recognized as a first-line treatment option for the management of chronic hepatitis B infection in both treatment-naive and treatment-experienced patients.