The hepatitis C virus (HCV) was identified as the major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis throughout the world. It is an enveloped virus with a plus-strand RNA genome encoding a polyprotein of about 3,010 amino acids. This polyprotein is cleaved co- and posttranslationally into mature viral proteins by host cell signal peptidases and 2 viral enzymes designated the NS2-3 proteinase and the NS3/4A proteinase complex. It is assumed that virus replication takes place in a membrane-associated complex containing at least 2 viral enzymatic activities: the NS3 nucleoside triphosphatase (NTPase)/helicase and the NS5B RNA-dependent RNA polymerase (RdRp). Based on their important role for the viral life cycle and the wealth of information available for related cellular and viral proteins, the NS3/4A serine-type proteinase complex, the NS3 NTPase/helicase and the NS5B RdRp are the most attractive targets for development of HCV-specific antiviral therapies. This review will summarize our current knowledge about structure and function of these proteins and describe approaches pursued to identify effective antiviral compounds.