Hepatitis C virus (HCV) is a common pathogen with an estimated 170 million people infected worldwide in the year 2000, unambiguously identified in 1989 as the major etiological agent responsible for post-transfusion non-A and non-B hepatitis. HCV infection is often benign or subacute initially, but many patients develop chronic liver damage 1-3 decades after initial contraction. At present, no vaccine or broadly effective therapy for all genotypes of HCV is available, with development hindered by lack of appropriate experimental systems (e.g., limited chimpanzee use, no efficient cell culture system for virus propagation). Despite these obstacles, molecular biology (including the 1989 cloning of HCV) has identified promising drug development opportunities, such as inhibitors of HCV replicative enzymes (protease, helicase, polymerase) and genetic approaches (ribozymes, antisense oligonucleotides). While recent reviews outline current and emerging therapeutic approaches to HCV infection, little attention has been paid to the design and development of virus-targeted drugs. This article places the drug design and development of hepatitis C genotype 1 therapeuticals into perspective, outlining the available targets and the ligands that currently display activity against these targets.