The effect of interferon alfa against hepatitis C virus has been well documented. However, clinical efficacy is low due to the short interferon residence in the body. To prolong half-life, interferon molecules have been bound to the biologically inert polymer, polyethyleneglycol. Pegylated interferons exhibit a longer residence time with an improved clinical efficacy, although the rate of therapeutic failure is still important. Addition of ribavirin to interferon, either pegylated or not, significantly increases efficacy. Therefore, the combination of a pegylated interferon with ribavirin has become the standard treatment of chronic hepatitis C. As the efficacy and safety of such combinations are not yet optimal, different drugs, including other types of long-acting interferons and ribavirin analogs, are presently been investigated.