Treatment with interferon alfa combined with ribavirin is successful in approximately 40% to 45% of patients with chronic hepatitis C viral infection (HCV). However, response rates are disappointing in patients who are difficult to treat, such as those infected with HCV genotype 1, high viral load, or advanced liver fibrosis. In addition, low tolerability and significant side effects of therapy frequently lead to dose reduction and treatment discontinuation, decreasing response rates further. Thus, investigation of new treatment options and innovations for chronic HCV infection are vital. This review describes recent advances in the treatment of HCV infection with PEGylated interferon (interferon modified with polyethylene glycol [PEG] ) combined with ribavirin.