The article provides a comprehensive overview of the natural history of hepatitis C virus (HCV) infection, emphasizing its impact on chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). HCV is a leading cause of chronic liver disease and the most common indication for liver transplantation in many countries. Despite a decline in incidence over the past decade, an estimated 170 million people worldwide are chronically infected, comprising 3% of the global population. The rate of chronic HCV infection is influenced by factors such as age, gender, race, and viral immune response, with 75%-85% of infected individuals progressing to chronic infection. The progression to cirrhosis is highly variable and influenced by alcohol consumption, age at infection, liver biopsy findings, coinfections, and comorbid conditions. Approximately 10%-15% of HCV-infected individuals will develop cirrhosis within 20 years, and those with cirrhosis are at increased risk of HCC. Understanding the natural history of HCV is crucial for effective management, treatment, and counseling of infected individuals. The article also discusses the routes of transmission, acute and chronic phases of HCV infection, extrahepatic manifestations, and future research directions.The article provides a comprehensive overview of the natural history of hepatitis C virus (HCV) infection, emphasizing its impact on chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). HCV is a leading cause of chronic liver disease and the most common indication for liver transplantation in many countries. Despite a decline in incidence over the past decade, an estimated 170 million people worldwide are chronically infected, comprising 3% of the global population. The rate of chronic HCV infection is influenced by factors such as age, gender, race, and viral immune response, with 75%-85% of infected individuals progressing to chronic infection. The progression to cirrhosis is highly variable and influenced by alcohol consumption, age at infection, liver biopsy findings, coinfections, and comorbid conditions. Approximately 10%-15% of HCV-infected individuals will develop cirrhosis within 20 years, and those with cirrhosis are at increased risk of HCC. Understanding the natural history of HCV is crucial for effective management, treatment, and counseling of infected individuals. The article also discusses the routes of transmission, acute and chronic phases of HCV infection, extrahepatic manifestations, and future research directions.