Summary. Hepatitis C virus (HCV) infection represents a major health problem, being a leading cause of cirrhosis and liver transplantation worldwide. Viral eradication achieved by Peginterferon and Ribavirin therapy is the only therapeutic option that can prevent fibrosis progression in chronic hepatitis and liver-related complications in cirrhotic patients. Unfortunately, the occurrence of potentially serious side effects argues against universal treatment of HCV-infected patients. Indeed most scientific societies suggest that eligibility for therapy be based on baseline factors, the so called clinical drivers for treatment eligibility. Current international guidelines recommend focusing on the severity of liver disease, likelihood of treatment response in terms of chances of sustained virological response (SVR) to antiviral therapy and risk of serious adverse events when making treatment decisions. However, evidence exists that treatment may benefit also patients with mild fibrosis and that baseline predictions of a SVR are inaccurate because of the key role of HCV kinetics while on-therapy. An extended treatment programme is further supported by the fact that an increase in the number of patients treated would ultimately result in a long-term reduction of liver-related deaths.