Summary. We systematically reviewed the evidence for long-term effectiveness and cost-effectiveness of antiviral treatment in patients with chronic hepatitis C. We performed a systematic literature search on the long-term effectiveness and cost-effectiveness of AVT in hepatitis C (1990–March 2007), and included health technology assessment (HTA) reports, systematic reviews, long-term clinical trials, economic studies conducted alongside clinical trials and decision-analytic modelling studies. All costs were converted to 2005€. Antiviral therapy with peginterferon plus ribavirin in treatment-naïve patients with chronic hepatitis C was the most effective (3.6–4.7 life years gained [LYG]) treatment and was reasonably cost-effective (cost-saving to 84 700€/quality adjusted life years [QALY]) when compared to interferon plus ribavirin. Some results also suggest cost-effectiveness (below 8400€/(QALY) of re-treatment in nonresponders/relapsers. Results for patients with persistently normal alanine aminotransferase (ALT) levels or with special co-morbidities (e.g. HIV) or risk profiles were rare. We conclude that antiviral therapy may prolong life, improve long-term health-related quality-of-life and be reasonably cost-effective in treatment-naïve patients with chronic hepatitis C as well as in former relapsers/nonresponders. Further research is needed in patients with specific co-morbidities or risk profiles.