Modification of the pharmacokinetic profile of interferon-alfa (IFNalfa) through pegylation (addition of a polyethylenglicol molecul) has resulted in a marked improvement of drug efficacy for the treatment of infection due to hepatitis C virus. Two pegylated derivatives of IFNalfa are available: PEG-IFNalfa-2a, with a 40 kDa polyethylenglicol molecule of branched structure, and PEG- IFNalfa- 2b, with a 12kDa linear PEG. Both compounds have slower absorption, more reduced distribution and lower elimination rate than the respective non- pegylated IFNalfa, which assures that concentrations appropriate to inhibit viral replication are maintained during longer periods of time, thus a allowing administration once a week, In addition to archieving greater therapeutic efficacy, the adverse effects related to excessive Cmax are reduced, the risk of therapeutic failure is decreased by eliminating the intervals of inefficient plasma levels, and the uncomfortable thrice weekly injection regimens are avoided. The current recommendations include the use of a combination therapy with pegylated IFNalfa and ribavirin as the standard treatment. However, further research is required to archieve dosage optimization of pegylated IFN and rebavirin according to the patientś characteristics and to evaluate the efficacy and safety of this combined theraphy for difficult- to- treat patients.