Hepatitis B Virus (HBV) infection remains an important cause of liver disease in renal transplant (RT) recipients and the outcome of HBV infected RT recipients is less favorable than that of noninfected RT recipients. The concern about graft loss induced by interferon (IFN) therapy precludes its use; lamivudine, a second-generation analog, has been recently approved for the treatment of hepatitis B and promises to be highly effective in this setting. Several uncontrolled trials have reported a high rate of biochemical (ranging between 80% and 100%) and virological (ranging between 67% and 100%) response in RT recipients, comparable to immunocompetent patients. Lamivudine has an excellent safety profile in RT recipients. However, the emergence of viral mutations leading to resistance has been reported during lamivudine therapy in RT recipients. In addition, numerous issues remain to be clarified about lamivudine use after RT including the management of viral resistance, the role of HBV genotypes in the response to lamivudine, and the duration of therapy and response. The combination of newer nucleoside analogues with lamivudine, analogous to HIV, may further improve the efficacy of antiviral therapy against HBV after RT.