Due to the side effect profile of pegylated interferons interferon treatment has become the holy grail of drug development for chronic hepatitis C. The precise role of interferon in treatment of hepatitis C is not fully understood, besides its antiviral effects interferon is an immune modulator. Nevertheless, recent proof of concept studies indicated, that cure of chronic hepatitis C can be achieved without interferon. Various compounds achieved this goal, like the polymerase inhibitor PSI 7977, the combination of NS5a inhibitor (daclatasvir) and a protease inhibitor (asunaprevir) and the cyclophillin antagonist alisporivir. Various other combinations are investigated currently. Providing that phase 3 studies will confirm these exciting data, direct acting antivirals or host targets will replace peginterferon/ribavirin combination therapy.