Year 201X will see a huge battle against hepatitis C virus (HCV) infection. HCV, a leading cause of end stage diseases and hepatocellular malignancies, is a negative legacy of the past in many regions worldwide, and has long been refractory to conventional treatments. The most effective peginterferons and ribavirin-based antiviral therapies can eliminate the virus in only half of patients treated, and the treatments are often poorly tolerated. Recently, the development of an HCV cell culture system has become a turning point of basic research. At present, novel therapeutic agents with different mechanisms of action are under development or on clinical trials. Some of these drugs have been proven to be effective when used with the conventional treatments, and may constitute antiviral therapies without being used in combination with interferons. This article reviews the current status of preclinical drug development, ongoing clinical trials, and near future perspectives in the field of HCV therapeutics.