Despite the existence of effective prophylactic vaccines, hepatitis B virus (HBV) infections remain a major public health problem. It has been estimated that about 370 million people are chronically infected with this virus worldwide. These individuals act as a reservoir for viral spread and chronic infection also increases the risk of liver diseases, such as cirrhosis and hepatocellular carcinoma. Current antiviral therapies fail to control viral replication in the long term in most patients. Viral persistence has been associated with a defect in the development of HBV-specific cellular immunity. The limitations of the current available therapies underline the need for alternative therapies. Specific immunotherapeutic strategies target not only the induction or stimulation of CD4(+) and CD8(+) T-cell responses but also the induction of proinflammatory cytokines capable of controlling viral replication. Therapeutic vaccination has been extensively studied in chronic hepatitis B (CHB) based in the properties of hepatitis B surface antigen (HBsAg) and taking advantage of its previous use in preventive vaccination. In this sense, pioneer studies were carried out employing HBsAgbased vaccines, including prophylactic commercial vaccines and HBsAg-based formulations with novel adjuvants. The results and general knowledge coming from these studies are discussed in the present review. The decision on developing new generations of vaccines including new antigens or formulations should take into account the experience with HBsAg-based vaccine formulations in order to decide about changing the vaccine antigen or adding new antigens to improve the composition.