The hepatitis C virus was first identified in 1989. It causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Global anti-HCV prevalence is 1–3%. Contaminated blood product, dirty needles and instruments, and injection drug use are the main parenteral routes of transmission. Cultural practices, such as acupuncture, tattoo, body piercing and scarring, also play a role. Universal precaution is the mainstay for prevention before vaccine is developed. Therapy for chronic hepatitis C (CHC) with interferon (IFN) is not satisfactory. Non-response and early relapse reduce sustained response (SR). In 1997, National Institute of Health consensus recommended IFN therapy only for selected patients with compensated CHC, raised ALT and moderate to severe histologic disease activity; 15–20% SR is expected. Major advances in CHC therapy is combination therapy. Ribavirin in combination with IFN significantly increases SR to 30–40%. Even patients with high viral load, genotype 1, significant fibrosis or cirrhosis respond better. EASL and APASL Consensus in 1999 recommended IFN-ribavirin combination as the first line therapy. Recent data on pegylated IFN showed very encouraging results. Combined with ribavirin, 60% SR was achieved. It benefits patients with severe bridging necrosis and also cirrhosis. However, 23–27% of patients receiving combination therapy with either IFN type, experienced adverse events and required therapy discontinuation. Many important issues remained unsolved. Therapy for children, the elderly, patients with comorbidity and extra–hepatic syndromes need to be addressed. Therapy is too expensive and not affordable to the majority of patients in developing countries.