Hepatitis C virus (HCV) causes acute and chronic hepatitis by targeting the liver hepatocyte for infection and destruction. The standard treatment for chronic HCV infection is pegylated interferon plus ribavirin. Unfortunately, the sustained response rate and associated toxicity with this treatment are far from ideal; more effective and less toxic treatment regimens are needed. With more than 170 million people infected worldwide, there is an unmet medical need for new effective treatments. Recent advances in the understanding of the signaling pathways leading to the host antiviral response to HCV, the mechanisms used by HCV to evade the immune response, the development of cell culture models of HCV infection and the development of small molecule inhibitors of HCV have generated optimism that novel therapeutic approaches to control HCV will soon be available.