The Cochrane Collaboration has published a systematic review about the treatment chronic hepatitis C (CHC) with direct-acting antivirals (DAAs) concluding that there is no evidence either to confirm or to reject the premise that DAAs have any clinical effects and they also state that sustained virological response is an unreliable surrogate marker to assess clinical efficacy. Here we discuss the implication of the Cochrane Collaboration review at the light of the current knowledge of CHC clinical management and propose a framework for the future research.