Recently several randomized trials involving exclusively HCV 2 and 3 patients have explored the possibility of reducing the duration of therapy with PEG IFNs and ribavirin to 12-16 weeks. Among these, the largest studies (ACCELERATE, NORTH-C and NORDynamIC) have failed to demonstrate, by intention-to-treat analysis, that short treatment is non-inferior to the standard duration of 24 weeks originated by phase 3 trials. Even though obtaining univocal conclusions from these studies are difficult to obtain due to some critical differences (trial design, genotypes 2/3 ratio, rate of cirrhosis at baseline, ribavirin dose, assays to detect HCV-RNA etc), all have proved that a rapid virological response (HCV-RNA negative at 4 weeks) is the strongest predictor of SVR. Therefore, excluding risk factors for virological relapse at baseline, and identifying in the early phase of treatment, features related to a sustained response, the decision to reduce the duration of treatment to less than 24 weeks in HCV-2 and 3 patients can be response-guided appropriately. Ongoing studies will assess whether extended 48 week regimens can benefit non-RVR patients with HCV 2 or 3, especially those with more severe fibrosis.