Pegylated interferon therapy for the treatment of chronic hepatitis C virus provides significant increases in sustained virological response rates compared with standard interferons. Two pegylated interferons are now available and are used in conjunction with ribavirin to maximize response rates in infected patients. The two pegylated interferons, peginterferonalpha-2a and peginterferonalpha-2b, differ substantially in terms of their chemical and structural characteristics, pharmacokinetic and pharmacodynamic properties, and dosing and administration. A full understanding of the differences between the two drugs is important to maximize the clinical benefits. Controlled studies designed to characterize the effects of the two drugs on viral kinetics and sustained virological response rates are emerging and may help to shed additional light on the use of these compounds in patients with chronic hepatitis C.