OBJECTIVE To provide nurse practitioners with the information to manage patients with chronic hepatitis C (HCV) receiving a new combination drug therapy containing ribavirin and interferon alfa-2b. METHODS Reviews of clinical trial results including large multicenter trials, Centers for Disease Control and Prevention documents, data from the drug manufacturer. CONCLUSIONS This new therapy offers the potential for HCV remission or complete cure of the HCV infection. Although virologic responses are markedly improved with combination therapy, the side effects associated with combination therapy warrant regular patient monitoring, management, and medical intervention when clinically indicated. CONCLUSIONS Combination therapy does not significantly worsen the side effects associated with mono-therapy, which are predictable, manageable, and reversible. However, proper patient education, symptom management, vigilance for serious side effects, and monitoring of hematologic parameters are critical to patient outcome.