The goal of antiviral therapy in patients with chronic hepatitis B is to prevent, through persistent suppression of HBV replication, cirrhosis and hepatocellular carcinoma. Currently, seven drugs are available: IFN-alpha, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. The choice of the drugs should always take into consideration the clinical features of patients, the antiviral efficacy of each drug, the risk of developing resistance, the long-term safety profile, the method of administration and the cost of therapy. Ideal candidates for treatment are hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis B e antigen-negative patients with elevated levels of serum HBV DNA, abnormal alanine aminotransferase and histologic evidence of moderate or severe liver necroinflammation and/or fibrosis. Patients with compensated or decompensated cirrhosis should be treated, even if alanine aminotransferase levels are normal and/or serum HBV DNA levels are low, in order to prevent disease flare and to improve liver function.