The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in western countries. Chronic hepatitis C is highly heterogeneous and many patients present with a mild form of liver disease. Population-based studies have indeed demonstrated that around 50% of hepatitis C virus carriers have persistently normal ALT and two-third have mild histological liver lesions. Studies on the natural history of initially mild chronic disease indicate that the short-term outcome is always benign. However, progression of liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly in those cases who have elevated and/or fluctuating transaminase levels. Observational prospective studies and outcome modelling projections indicate that the risk of liver disease progression towards severe fibrosis/cirrhosis is minimal at 10-15 years in hepatitis C virus carriers with persistently normal ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol, coinfections and liver steatosis accelerate disease progression. On the basis of these findings, patients with initially mild chronic hepatitis C and elevated ALT should be proposed for antiviral therapy in the absence of contraindications.