Despite the improvements in HCV-therapy achieved in the last 20 years, the occurrence of high frequency of non-responders and of therapy-related side effects has lead to an ongoing interest in optimizing duration and dosage of current antiviral regimens as well as to the research and development of new antiviral treatment. Recently, the discovery of a system for in vitro HCV replication provided a useful tool for a better understanding of the viral life cycle followed by the discovery of new compounds that unlike classical drugs specifically target fundamental steps of this process. The aim of this review is to provide an update on the preclinical and clinical development of novel anti-HCV treatments targeting the first steps of the viral life cycle. The recent patents in this review article discuss the new perspectives in HCV therapy.