The drugs currently licensed for the treatment of hepatitis C are Peg-Interferon (PEG-IFN) and ribavirin. In recent years, the recommendation to treat hepatitis C virus genotype 2- and 3-infected patients with a fixed 800 mg/day dose of ribavirin in combination with PEG-IFN and for just 24 weeks has been challenged by the concept of tailoring the length of therapy according to on-treatment viral response. Therefore, the objective of the present review was to highlight the different designs of the studies on short treatment duration and the role of wk4-R as a predictor of sustained virological response after an abbreviated course of treatment. The secondary aim was to verify whether we had enough evidence to support the implementation of a short treatment course in subsets of patients with genotype 2 and 3 infection. We will also focus on how drug dosing may have influenced the outcome of treatment. To clarify reasons for discrepant results in the studies so far published, the recently discovered genetic variant near the interleukin 28B gene will be presented and its predictive role will be discussed. Finally, we will face the debated issue of whether the subset of patients with genotype 2 or 3 requires an extended treatment duration.