Treatment of chronic hepatitis C during the past years has shown a significant increase of the percentage of therapeutic response, mostly due to the availability of pegylated interferons. Nevertheless a proportion of patients, ranging from 15% to 60%, do not achieve the virus eradication after treatment, largely depending on viral genotype. Retreatment of non responders is recommended in those patients who have been treated with non-pegylated interferon. In these patients, the rate of antiviral response to retreatment depends on genotype, viral load, degree of histological damage, ethnicity and metabolic conditions, but also on patients' adherence to the therapy schedule. The probability of a sustained virological response after retreatment ranges from 8% to 26%. To improve the efficacy of retreatment, either interferon and/or ribavirin dosage have been increased, either other antiviral drugs have been added to combination therapy. Although these new strategies have produced variable results, they remain the cornerstone of retreatment in view of forthcoming new antiviral drugs.