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Therapeutic vaccination of chronic infectious diseases has been extensively explored because of its possible contribution to their eradication. In particular, therapeutic vaccination of hepatitis B virus chronic infections is especially interesting since this disease is characterized by a sustained necro-inflammatory process of the liver that may evolve into more severe conditions including cirrhosis and hepatocellular carcinoma. The basic role of the immune system in the healing process of this chronic infection suggests that it offers a favorable setting for immunotherapeutic treatments, either spontaneously or as a result of antiviral therapy. However, no vaccine has been able to cure this or any other chronic infection in spite of the large number of vaccine candidates tested. The knowledge of the liver as a lymphoid organ and the limited advances of therapeutic vaccination demand more thorough analyses within the rationale of current vaccine candidates. In the last ten years there has been an increased knowledge of innate immunity and intra- and extra-hepatic signaling mechanisms, to support a rational design of vaccine strategies. The high costs and low effectiveness of conventional treatments, and the large amount of chronic carrier patients for this virus, indicate a favorable setting for the development of immunotherapeutic products against chronic hepatitis B. It is possible to predict that adjuvant strategies that take into account the properties of the liver as a lymphoid organ would have an impact in the development of this new field of therapeutic vaccines. [ABSTRACT FROM AUTHOR]