In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN). The first clinical trial of recombinant IFN-alpha in patients with chronic hepatitis C was published in 1986. This article reviews the classification of IFNs, IFN production during viral infections, IFN signaling pathways and the mechanisms of their antiviral and immunomodulatory properties. Hepatitis C virus infection treatment is currently based on the combination of pegylated IFN-alpha and ribavirin. The pegylated IFN-alpha molecules are described, as well as the putative mechanisms of action of ribavirin. Current treatment guidelines are discussed and new results suggesting that the treatment schedule should be tailored to the early virological response during therapy are presented. Finally, insights into new hepatitis C drug developments are given.