NK cells play important roles in every stage of HCV infection from protection against infection in IDUs to prediction of antiviral success or failure with IFN-based therapies. Several NKRs and functional properties of NK cells have been implicated. Their association with natural history, stage of infection and treatment outcome are shown. KIR, killer immunoglobulin-like receptor; HLA, human leukocyte antigen; IFN-γ, interferon-γ; TRAIL, TNF-related apoptosis-inducing ligand; NCRs, natural cytotoxicity receptors; SVR, sustained virological response.