The estimated prevalence of hepatitis C virus (HCV) infection is 2%, representing 123 million infected individuals worldwide. HCV infection burdens public health in relation to hepatic (cirrhosis and its complications in 20% of patients) and extrahepatic (vasculitis) complications, and lessens quality of life. Major progress has been made in the last two decades for the diagnosis and treatment of HCV, including more appropriate screening strategies for HCV infection (improved sensitivity of serological and virological tests); a better evaluation of the impact of chronic HCV infection on the liver (semi-quantitative scoring systems of necro-inflammation and fibrosis on liver biopsy, non-invasive evaluation of fibrosis with biochemical markers and elastometry); and improved therapeutic regimens. This progress provides a better definition of who to treat (clinical impact or significant fibrosis); how to treat; tailoring therapies for doses and durations of the pegylated interferon plus ribavirin combination according to virological (mainly genotype and early viral kinetics, but also baseline viral load) and hosts factors (fibrosis, immune status, weight); and how to monitor efficacy and tolerance of therapy. The progress has now resulted in a 50% rate of complete HCV eradication, ranging 45 - 90% according to the genotype and especially in those patients with early viral response. New therapies, specifically HCV protease or polymerase inhibitors, in combination with pegylated interferon, or more potent and less toxic new formulations of interferons or ribavirin, will increase these encouraging results in the future.