Virus-encoded enzymes of hepatitis C virus (HCV) were identified from its genome sequence. This allows application of drug discovery strategies which rely on inhibition of enzymes unique to HCV. Discovery of high-affinity inhibitors is facilitated by knowledge of the target enzyme's three-dimensional structure. For development of inhibitors of the HCV helicase, which belongs to a class of enzymes for which little structural information is available, the impact of structural information on the drug discovery process is greater than for targets belonging to well-characterized classes of enzyme. Here the structure of the HCV helicase is described. Regions required for enzymatic activity, which are also the preferred sites of drug interaction, are highlighted.