Hepatitis C is a leading indication for transplantation and a common cause of liver-related death worldwide. Treatment for hepatitis C has evolved from interferon therapy alone, which yielded relatively poor response rates compared with the currently recommended and more effective combination of pegylated interferon and ribavirin. Factors such as hepatitis C viral genotype, pretreatment viral load, race, renal function, degree of hepatic fibrosis, and comorbid conditions such as HIV coinfection have clinical importance in that they influence viral kinetics, which play a large role in determining a sustained response to therapy or virologic "cure." However, the goal of therapy is to reduce liver-related morbidity and mortality by decreasing rates of progression or improvement of fibrosis, reducing risk of hepatocellular carcinoma, improving posttransplant graft and patient survival, and resolving or improving some of the extrahepatic manifestations of hepatitis C. Studies generally infer long-term success from the more tangible goal of sustained viral suppression; however, increasing data suggest that effective therapy does result in decreased morbidity and mortality. Given the heterogeneity of patients who are infected with hepatitis C, treatment decisions should be specifically tailored to each individual patient on the basis of their predisposing conditions and anticipated clinical outcomes.