In 2009, genome-wide association studies identified key roles for IL28B and ITPA polymorphisms in predicting HCV treatment outcomes using pegylated interferon-α and ribavirin therapy. The IL28B polymorphism is strongly associated with antiviral efficacy of interferon-based HCV therapy, as well as with the spontaneous clearance of acute HCV infection. Very recently, it was proposed that IL28B polymorphisms actually tag a functional variant that affects the novel IFNL4 gene. Two functional ITPA variants determine the risk of ribavirin-induced hemolytic anemia. Personalized medicine is now a reality for chronic HCV patients, and IL28B genotyping has been incorporated into the clinical algorithm for individuals considering antiviral therapy.