The ultimate goal of hepatitis C virus (HCV) treatment is the eradication of the virus. Ongoing research continues to add to knowledge of the HCV life cycle, revealing new potential viral and host targets for the development of therapy. Understanding of HCV was initially hampered by the inability to achieve viral replication in cell culture. Advances such as the HCV replicon and complete cell culture systems, however, have permitted rapid growth in knowledge and accelerated testing of candidate antiviral agents. Among potential targets are viral entry factors, including scavenger receptor type B1 (SR-B1) and CD81, as well as neutralizing antibodies against the viral glycoproteins. Popular targets related to translation and replication are the NS3/4A protease (inhibited by telaprevir and boceprevir) and the NS5B polymerase, as well as the NS2/3 autoprotease, the NS3 helicase, and nonenzymatic targets such as NS4B and NS5A proteins. Host targets are also available, including microRNAs and cyclophilins. This article summarizes a presentation by Charles M. Rice, PhD, at the IAS–USA live continuing medical education course, Management of Hepatitis C Virus in the New Era: Small Molecules Bring Big Changes, held in New York City in April 2011.