Weekly injections with pegylated-IFNa (PegIFN) combined with daily ribavirin (RBV) are still the standard of care for chronic hepatitis C in most of the world. Sustained virological response (SVR) of 40–50% for patients infected with HCV genotypes (GT) 1 or 4 and 70–90% for genotypes 2–3 are achieved with this regimen. Triple therapy, registered in both the EU and USA, utilizing the first-generation direct protease inhibitors is able to increase the SVR rates to 75%, but its use is restricted to patients infected with HCV GT1. Additional limitations include challenging dosing schedules, complex treatment algorithms, limited efficacy in patients with previous null response to PegIFN/RBV therapy and additional side effects. There is also an important need for more effective antiviral therapy for difficult-to-treat populations with PEG-IFN intolerance, particularly those with cirrhosis and non-responders to previous therapies. All-oral, IFN-free therapies are an evolutionary step for future anti-HCV therapies. Initial results of clinical studies conducted during the last year give hope for ‘a pill for HCV’ at least in selected CHC populations. In 2013 several clinical trials of all-oral anti-HCV therapies had been completed, first all-oral combination submitted for registration and some conclusions could be drawn. However, there is not yet a clear direction for IFN-free therapies in treatment naïve patients or more complex non-responders.