Hepatitis B virus (HBV) is the major cause of acute and chronic hepatitis which could lead to hepatocellular carcinoma. Currently, interferon- ? and nucleosidic inhibitors of HBV reverse transcriptase, polymerase, lamivudine (3TC), adefovir and entecavir are the only drugs approved for the treatment of chronic HBV infection. However, interferon-?-produces many side affects with partial efficacy less than 30% of the chronic carriers responding to treatment. In addition, about 50% of the patients who respond positively to interferon- ? treatments are known to suffer recurrence of the viremia after cessation of the treatment. In contrast, 3TC has more universal applicability and is able to reduce the viral load very rapidly. Complete and sustained suppression of viral replication remain the most important goal in the treatment of patient with chronic (HBV) infection. Nucleoside and Nucleotide analogues have greatly improved the disease outcome for these patients and have also prevented hepatic decompensation or the development of hepatocellular carcinoma. Therefore, there is need for drugs that directly inhibit HBV production. Most compounds explored so far are nucleoside analogs.