Clevudine is a new potent hepatitis B polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients, which may be related to its pharmacokinetics. The aim of this brief review was to evidence the efficacy and safety of this drug for the treatment of chronic hepatitis B virus-related hepatitis. The review of the literature evidences that clevudine (30 mg/d, orally) is a potent inhibitor of hepatitis B virus replication and well tolerated with rare mild adverse effects. No resistance to clevudine was detected. Other studies are needed to evaluate the efficacy of this drug in monotherapy or in combination with other nucleoside/nucleotide analogs (lamivudine, adefovir dipivoxil, entecavir, and emcitrabine) for the treatment of patients with chronic hepatitis B.