The development of new antiviral therapies in the treatment of hepatitis C virus (HCV) is reviewed, including a discussion of the potential advances that this treatment will bring. Data from new molecules in Phase I and II clinical trials, specifically polymerase and protease inhibitors, will be discussed. The potential for resistance has been reported when these have been used as monotherapy. However, their use in combination with pegylated interferon, particularly in the presence of ribavirin, has resulted in significant improvements in antiviral activity. Preliminary studies have confirmed that the new molecules are well tolerated and further clinical studies are underway to evaluate their efficacy. Nevertheless, because of its critical role at all stages of therapy, pegylated interferon is likely to remain the cornerstone of HCV therapy.