Despite universal vaccination, chronic hepatitis B (CHB) continues to be a major health burden worldwide, with an estimated 350-400 million people infected with the virus. Over the past decade, rapid progress has been made with regards to antiviral therapy for CHB, from conventional interferon to pegylated interferon, and with the earliest oral agent lamivudine to the current, more potent drugs such as entecavir and tenofovir. There have also been new developments in the diagnostic and monitoring tools for CHB. Qualitative hepatitis B surface antigen (HBsAg) testing has been used to diagnose patients infected with CHB. More recently, quantitative HBsAg titers have been used to predict treatment outcome when measured at baseline or early into treatment. The progress on the use of hepatitis B virus (HBV) DNA levels has been more rapid. Serum HBV DNA levels have been shown to be important in the natural history of CHB infection, with higher levels being significantly associated with the development of cirrhosis and hepatocellular carcinoma. For patients receiving antiviral therapy, the baseline and early on-treatment HBV DNA levels are important in determining treatment outcomes. Monitoring of HBV DNA levels during therapy will allow for early detection of drug resistance. The end-of-treatment and post-treatment HBV DNA levels have been demonstrated to be important indicators of treatment success and relapse, respectively. With newer and more powerful antiviral agents, and with the development of quantitative assays that are highly sensitive, further studies are needed to optimize the use of these tools and agents in the modern management of CHB.