Chronic hepatitis B virus (HBV) infection, affecting approximately 350 million people worldwide, is associated with significant morbidity and mortality. In the past 10 years, hepatitis B therapy research has led to a multitude of available antiviral therapies: IFN-alpha, pegylated IFN-alpha(2a), lamivudine, adefovir, entecavir, telbivudine and tenofovir. To further improve reductions in viral load and resistance profiles, development of new HBV therapeutic strategies has been an important focus. One such therapy is clevudine, an analogue of the beta-L configuration. Clevudine is already licensed in Korea for anti-HBV therapy (Bukwang Pharmaceuticals, Seoul, Korea). Unique to clevudine is its ability to maintain antiviral activity following discontinuation of therapy. Typically, hepatitis B treatment requires continuous therapy to prevent reactivation. Sustained response is uncommon except in hepatitis B antigen (HBeAg)-positive patients who developed HBeAg seroconversion. This article reviews chronic HBV and its therapy options. Specifically, it describes clevudine's potent and sustained antiviral activity as observed in vitro and in vivo.