Lamivudine is a potent, once-daily, oral antiviral therapy that is effective and well tolerated in most patient groups with chronic hepatitis B virus infection, including those with pre-core mutant infection. Studies to date show that lamivudine suppresses serum viral replication, causing reductions in serum hepatitis B virus (HBV) DNA and enhancing hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg plus presence of antibodies to HBeAg [anti-HBe]). Lamivudine also improves liver disease, as shown by normalisation of alanine transaminase (ALT) levels and reduced progression to cirrhosis. Lamivudine is effective in patients who are interferon (IFN) alpha naïve and in those who have failed to respond to IFN alpha, and it suppresses HBV in decompensated liver disease and in liver transplantation. Variants with mutations in the YMDD (tyrosine−methionine−aspartate−aspar-tate) motif may emerge with prolonged lami-vudine therapy, but most patients maintain clinical control. Lamivudine has a safety profile similar to that of placebo and it is better tolerated than IFN alpha. In conclusion, lamivudine represents a major advance in the therapeutic options available for the management of patients with chronic hepatitis B and should now be considered the drug of choice for most patients who require treatment. J. Med. Virol. 61:386–391, 2000. © 2000 Wiley-Liss, Inc.