According to the WHO, approximately 350 million people have chronic hepatitis B. Individuals with chronic hepatitis B have a highly variable and unpredictable clinical course and are at risk for developing cirrhosis and hepatocellular carcinoma. Lamivudine is the only oral antiviral agent approved for the treatment of patients with chronic hepatitis B.Lamivudine is useful in a wide range of patients with chronic hepatitis B and ongoing viral replication. In patients with compensated liver disease treated for 52 weeks in multicenter randomized, double-blind clinical studies, lamivudine 100 mg/day inhibited hepatitis B virus (HBV) replication, normalized ALT levels, produced significant reductions in hepatic necroinflammatory activity and halted the progression of fibrosis compared with placebo. Hepatitis B e antigen (HBeAg) seroconversion rates were also increased during treatment with the drug compared with placebo.In patients who continued to receive the drug after the completion of these trials, improvements in liver histology were maintained and HBeAg seroconversion rates increased in proportion to the duration of treatment.Pretreatment ALT levels were predictive of HBeAg seroconversion. In patients with baseline ALT levels ≥2-fold higher than the upper limit of normal, seroconversion rates were significantly higher than in those with lower baseline values.Data from 2 randomized studies indicate that sequential therapy with lamivudine for 8 weeks and then lamivudine plus interferon-α for 16 weeks provides no greater benefit than that of monotherapy with lamivudine for 52 weeks or interferon-α for 16 weeks.According to data from noncomparative studies, lamivudine 100 or 150 mg/day resulted in clinical stabilization, significant reductions in Child-Pugh-Turcotte scores and loss of HBeAg in many patients with decompensated liver disease. Moreover, some patients have been placed on inactive status for liver transplantation after treatment with the drug.Lamivudine-resistant HBV variants have been isolated from patients with chronic hepatitis B during treatment with lamivudine. The prevalence of these variants increases with the duration of treatment; however, their long term clinical significance has not been established.Lamivudine is well tolerated. The frequency of adverse events in lamivudine or placebo recipients was similar in a pooled analysis of clinical trial data. Nonetheless, patients must be monitored for the emergence of lamivudine-resistant variants and elevated liver enzyme levels (ALT flares).In a series of economic models, use of lamivudine was predicted to reduce the cost per case of cirrhosis prevented and increase mean life expectancy compared with use of interferon-α in the US. Other analyses, which incorporated a fixed drug budget scenario, concluded that use of lamivudine would increase the number of successfully treated patients by 2- to 3-fold compared with interferon-α, because of lower acquisition costs.In conclusion, lamivudine is useful in a wide range of patients with chronic hepatitis B and ongoing viral replication.