Hepatitis C virus genotype 4 (HCV-4) is the most common type of hepatitis C virus (HCV) in the Middle East and Africa, in particular Egypt. Since the development of new protease inhibitors, the response of HCV-4 to the standard regimen of treatment (pegylated interferon/ribavirin) lags behind other genotypes and has become the most resistant type to treat. The development of therapeutic strategies for all patients with HCV-4 whether they are naïve, have experienced a virological breakthrough, are relapsers or non-responders is still a considerable challenge. New types of interferon (Consensus Interferon, Y-shaped, Albinterferon…) and new direct action antiviral drugs (Nitazoxanide, Vit.D, other) may improve the treatment of patients with HCV-4. The IL28B CC polymorphism may be associated with sustained virological response.