In 2009, several different research groups simultaneously identified the polymorphisms close to IL28B gene as an important predictor of therapeutic response for chronic hepatitis C (CHC) patients receiving interferon-based treatment using approaches of genome-wide association studies. They also found that these genetic variations were strongly associated with the spontaneous viral clearance of hepatitis C virus (HCV) infection. Following these studies, ITPA gene variants were reported to affect ribavirin-induced anemia and therapeutic outcomes of CHC patients. All these lines of evidence usher in a new genomic era for the management of HCV infection. In this article, advances in recent genome-wide association studies regarding HCV infection, and their impacts on the management of CHC patients will be reviewed. In addition, the clinical usefulness of genomic variations on the addition of direct antiviral agents to current standard of care will be discussed.