End-stage liver disease related to chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation (LT) in the United States. Recurrence is almost universal, and HCV infection significantly impairs patient and allograft survival following LT. 1 The spectrum of histologic injury related to HCV recurrence is highly variable, ranging from mild histologic abnormalities to allograft cirrhosis in up to 30% of recipients by the fifth postoperative year. 2 Although this is an active and promising area of research, we currently cannot reliably identify patients who will develop progressive HCV recurrence. Thus, identifying variables before LT that predict more aggressive HCV recurrence is of importance, particularly in the context of donor organ shortage. The immune response is a critical determinant of clinical outcome in both the acute and chronic phases of HCV infection. 3 Liver injury secondary to HCV infection is thought to be immune-mediated and not to result from the direct cytopathic effects of the virus. 4,5 Considerable gaps exist in our understanding of how the immune response influences HCV recurrence post-LT. In this setting, the infection of an HCV-naı ¨ve allograft in some ways resembles acute HCV infection, and this suggests a role for innate immune mechanisms in recurrent HCV disease outcome. 6,7 In this issue of Liver Transplantation, Espadas de Arias and colleagues 8 contribute to our understanding of the potential role of natural killer (NK) cells in the antiviral immune response of LT recipients, adding important information to an emerging area of research.