Despite the presence of an effective prophylactic vaccine since 1982, more than 350 million people of the world are now chronically infected with hepatitis B virus (HBV). In one scenario, a considerable numbers of chronic HBV carrier would eventually develop serious complications like liver cirrhosis and hepatocellular carcinoma. In another, chronic HBV carriers would be permanent sources of HBV infection and transmit HBV to uninfected healthy individuals. Taken together, chronic HBV infection represents a major global public health problem, especially in the developing nations of the Asia and Africa, where most of the chronic HBV-carriers reside. Unfortunately, there is no good curative therapy approach for these patients. The prospect of treatment of chronic HBV infection by antiviral agents like type-1 interferons and lamivudine is not satisfactory due to their low efficacy, considerable side effects and high costs. Vaccine therapy, an immune therapy, has recently shown considerable optimism for treating patients with chronic HBV infection. In this review, we will first describe the pathogenesis of chronic HBV carrier state to provide scientific and ethical rationales of vaccine therapy in chronic HBV carriers. Next, we will summarize the information that has been compiled from ongoing clinical trials of vaccine therapy in chronic HBV carrier. Finally, we will discuss the mechanism of action of vaccine therapy in patients with chronic HBV infection and HBV transgenic mice, a murine model of chronic HBV carrier state. This information will be valuable for developing next generation therapeutic vaccines for the management of chronic HBV infection.