Therapy of chronic hepatitis C presently achieves 60% of sustained virological response, with clear on improvement of liver histology. Failure to eradicate HCV infection does not mean that the patient is non-responsive to therapy and indeed most patients improve biochemically and histologically. The objective of maintenance therapy is therefore to reduce fibrosis progression and its complications. Meta-analysis of 4 registration pivotal trials revealed that 40% of patients who failed to clear HCV at the end of therapy, improved histologically. 3 large long term prospective studies in mostly advanced patients have also addressed the issue of maintenance therapy: HALT-C, COPILOT, EPIC 3. Interim analysis at 2 years of the COPILOT study in particular reveals that only 20% patients receiving low dose peg-interferon versus 39% in the placebo colchicine group reached complication end points. Prospective and retrospective studies, controlled or not, do also indicate a significant trend towards reduced incidence of HCC in patients receiving long term interferon therapy. Potent new anti-HCV small molecules will soon become available and will undoubtedly increase dramatically the cure rate. It is critical therefore for the moment to protect as many patients as possible from irreversible deterioration.