Hepatitis C Virus (HCV) infects 170 million people worldwide. Current standard treatment with pegylated interferon alpha (IFN?) and ribavirin cures only 50% patients. Therefore, developing a prognostic tool that can be used to predict whether a given patient will respond to therapy is of great importance clinically. This book describes a novel predicting method based on a subset of 18 hepatic gene expression that predicts who will respond to therapy with an accuracy of 96%. A new ubiquitin-like signaling pathway (ISG15/USP18) was revealed to be involved in interferon resistance. Furthermore, preactivation of interferon signaling pathway leading to the increased expression of some interferon stimulated genes (ISGs) in hapatocytes correlates with treatment non-response. Data presented in this book help us understand novel mechanisms of interferon resistance in HCV infected patients. This book should be especially useful to professionals in HCV and personalized medicine field.