Introduction: About 2.35% of the world population can be infected with hepatitis C virus (HCV) responsible for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently available interferon-based medication is successful in up to 75% of the patients infected with HCV genotypes 1, 2 or 3 and lower efficacy in other genotypes. Unfortunately sustained virologic response (SVR) rate in genotype 1 infected non-responders to previous therapy with advanced hepatic fibrosis even after retreatment with the first generation direct acting antivirals (DAA) is about 40% only. Areas covered: The second generation DAA, which have recently been submitted for registration (Sofosbuvir and Simeprevir) still need combination with PegIFNα and RBV in patients infected with HCV genotype 1. There is a need for more effective antiviral therapy for difficult to treat patients who are interferon intolerant, developed liver cirrhosis or non-responders to previous therapies. Therefore, IFN-free regimens are step for future therapies consisting of combinations of novel investigational DAA and host targeting agents. Expert opinion: The introduction of novel DAA with a good safety profile and high barrier to resistance can lead to SVR rates exceeding 90% in treatment naïve patients and non-responders to previous therapy infected with different genotypes.