Therapeutic vaccines are currently developed for chronic viral infections, such as human papillomavirus (HPV), human immunodeficiency virus (HIV), herpesvirus and hepatitis B (HBV) and C (HCV) virus infections. As an alternative to antiviral treatment or to support only partially effective therapy a therapeutic vaccine shall activate the patient's immune system to fight and finally control or ideally even eliminate the virus. Whereas the success of prophylactic vaccination is based on rapid neutralization of the invading pathogen by antibodies, virus control and elimination of infected cells require T cells. Therefore, induction of a multi-specific and multifunctional T-cell response against key viral antigens is a paradigm of therapeutic vaccination – besides activation of a humoral immune response to limit virus spread. In this review, we describe options to develop a therapeutic vaccine for chronic viral infections using HBV as a promising example.