Hepatitis C virus (HCV) is an infectious disease affecting primarily the liver. Worldwide, more than 170 million persons have HCV infection, of which 71 million have chronic infection. Egypt faces the largest burden of HCV infection in the world with 14.7% prevalence of chronic HCV infection. HCV is a major risk factor for developing hepatocellular carcinoma (HCC) through different pathogenetic pathways. Direct-acting antiviral therapy revolutionized the treatment of chronic hepatitis as this therapy can cure more than 95% of persons with HCV infection. This review aims to elucidate the epidemiology, genotypes, and modes of transmission of HCV and illustrates different scoring systems used for assessment of grade (severity) of necroinflammation and stage of fibrosis as evidence of disease progression. This has important prognostic and therapeutic implications.