Abstract: Hepatitis C virus (HCV) infection is one of the global public health issues. Approximately, 130-150 million individuals are chronically infected worldwide and a quarter of these patients are at increased risk of developing liver cirrhosis, hepatocellular carcinoma and even liver failure. A complete eradication of the virus is one of the most important treatment goals for antiviral research. From the point of view of medicinal chemistry, we summarize and discuss current endeavors towards the discovery and development of novel inhibitors with various scaffolds or distinct mechanisms of action.