BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efifcacy and safety proifle in hepatitis B virus (HBV) infection have already been studied in detail worldwide. This review summarizes the efifcacy of lamivudine, adefovir, entecavir and newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B in different clinical situations. DATA SOURCES: An English-language literature search using OVID and MEDLINE was performed and a total of 40 articles on the treatment of chronic hepatitis with nucleos(t)ide analogues were selected. RESULTS: Nucleos(t)ide analogs such as lamivudine, adefovir and entecavir are well tolerated and induce a decrease in serum HBV-DNA levels associated with normalization of serum alanine aminotransferase (ALT) levels. But their sustained response with HBeAg to anti-HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response is maintained during therapy which needs to be continued indeifnitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reactivation of hepatitis B. However, drug resistant mutations can be induced in long-term treatment. Other newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are still under phaseⅡorⅢclinical trials. CONCLUSIONS:Nucleos(t)ide analogs play an important role in the therapy of hepatitis B now and in the future. Lamivudine is limited by the frequent emergence of drug-resistant (HBV) mutants (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation andwild type. Therapeutic options against hepatitis B virus remain a major clinical challenge.