Chronic hepatitis C virus (HCV) infection results in scarring of the liver and ultimately cirrhosis, liver failure, and hepatocellular carcinoma. One goal of hepatitis C treatment is eradication of the virus, which typically leads an improvement in liver fibrosis. Combination therapies that include interferons (IFNs) and ribavirin increase the rate of a sustained virological response (SVR). Moreover, triple therapy containing direct acting antiviral agents (DAAs) dramatically improves SVR rate, particularly in patients infected with high titer genotype 1b HCV. However, these treatments are accompanied by many serious adverse effects, such as cytopenia and depression, specifically in the elderly. Natural human IFNβ and ribavirin combination therapy is currently available in Japan and is associated with a lower incidence of side effects as compared with IFNα (Peg-IFNα) and ribavirin. Therefore, clinicians should bear IFNβ and ribavirin combination therapy in mind as a well-tolerated and effective option for chronic hepatitis C treatment.