Hepatitis C is a heterogeneous disease whose natural history is controversial and perplexing. However, it can be a pernicious disease and is responsible for considerable mortality and morbidity. More than 80% individuals infected with the hepatitis C virus (HCV) develop chronic infection; the remaining 10–20% develop spontaneous clearance with natural immunity. The majority of patients who develop chronic HCV infection are asymptomatic; but 60–80% develop chronic hepatitis as indicated by elevated ALT; around 30% maintain normal ALT. One-third of chronically infected patients develop progressive liver injury, fibrosis and cirrhosis over a period of 20–30 years, and 15% develop hepatocellular carcinoma. Acquiring infection after the age of 40 years, male sex, excessive alcohol consumption, HBV or HIV co-infection and the immunosuppressive state have been identified as factors associated with progression of fibrosis and development of cirrhosis. The relationship between virus load, HCV genotype I and quasispecies variability and progression of live disease is controversial. In the present study on 141 patients with chronic HCV infection and established chronic liver disease, the median time to develop cirrhosis was 20 years. Progression to cirrhosis was faster (16 vs 20 years) in those who acquired infection after the age of 35 years, and in immunosuppressed patients (8 vs 21 years), whereas diabetes, sex and HBV co-infection were not associated with faster progression.