Conventional pharmacotherapeutic approaches to the management of chronic hepatitis B virus (HBV) infection are compromised by drug resistance and a failure to achieve sustained HBV DNA suppression. Low rates of seroconversion to hepatitis B e antigen-negative status and loss of hepatitis B surface antigen, as well as the potential for the development of adverse effects, are additional problems. Two agents, entecavir and the pegylated interferon (peginterferon) alpha-2a, have recently been added to the therapeutic armamentarium for the management of chronic hepatitis B (CHB). Data from clinical trials indicate that these newly licensed drugs may offer advantages over conventional treatments such as lamivudine and, possibly, adefovir. In addition, several novel agents in late-stage clinical development, specifically telbivudine and clevudine, have also shown encouraging results in patients with CHB infection. This review summarizes the current clinical experience with these new agents, focusing on data in Asian populations, and discusses the implications of the data for CHB management.