Infection with Hepatitis C virus (HCV) is a major cause of acute hepatitis and chronic liver disease. It affects more than 170 million people globally and is the leading cause of mortality due to an infectious agent in the US. The burden of HCV-associated disease is expected to rise over the next twenty years. Up until recently treatment of HCV was a combination of pegylated interferon alpha and ribavirin over a 48-week period. The addition of a protease inhibitor to the treatment regimen has improved efficacy and allowed for shorter treatment times however patients continue to suffer from the limitations and unbearable side effects attributed to interferon. In this work, we describe recent advances in the development of inhibitors to HCV that could be used as part of an interferon-free combination therapy.