Hepatitis C virus is an ever-increasing worldwide health problem with over 350,000 individuals succumbing to hepatitis C virus-related liver diseases each year. The ability to determine the outcome of an acute-phase illness may be useful in terms of implementing treatment strategies; however, to date, the predictive associations in the literature have centered around candidate gene analysis. Much greater advancements have been made in describing biomarkers from the activation of the host innate immune response, such as the interferon system, for prediction of treatment outcome in chronic hepatitis C with the advent of genome-wide association studies. Recent times has seen a major breakthrough in the field with the description of the IL28B genotype as an independent association factor for pegylated IFN-α2b/ribavirin treatment response. The ability to couple this with other easily measured biomarkers such as the interferon-stimulated gene CXCL10, serum concentration may make this predictive marker set very useful in the clinical setting.