The universal prevalence of hepatitis C virus (HCV) infection, which causes chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma, has become a significant health problem worldwide. Interferon-based therapies, the current standard, IFN-based therapies have limited efficacy and undesirable adverse effects. In addition, neither vaccination against HCV nor specific antiviral reagents for HCV are yet available. Thus, a major medical need still exists for novel and more efficacious anti-HCV reagents showing broad-spectrum clinical efficacy with enhanced tolerability. With the progress in our current understanding of the function and regulation of HCV gene products, the three-dimensional structures of virally encoded enzymes and the recent establishment of the HCV-replicon system, several pharmacological targets are being studied for HCV therapy, including cellular receptors mediating HCV entry, factors facilitating HCV replication and assembly, and intracellular pathways. Recently developed mouse models will be very helpful in evaluating the in vivo efficacy of novel antiviral reagents. Currently many novel antiviral drugs are under evaluation in clinical trials. This review will comprehensively discuss the current treatment options and various novel antiviral reagents available. Ongoing clinical studies of promising lead drugs are also reviewed.