Evaluation of: Nakayama Y, Plisch EH, Sullivan JM et al. Role of PKR and type I IFNs in viral control during primary and secondary infection. PLoS Pathog. 6(6), e1000966 (2010). During acute viral infections, innate antiviral immunity has been extensively studied for its ability to inhibit and/or control viral replication while priming the adaptive immune system. Recently, these processes have been studied for their role in assisting adaptive immunity to effectively clear or control viral rechallenge. The paper under evaluation introduces the concept that functional innate immune mechanisms such as dsRNA-activated protein kinase (PKR) and type I interferons are critical in controlling viral replication during secondary lymphocyte choriomeningitis virus infection. Elegant adoptive transfer studies revealed that during lymphocyte choriomeningitis virus secondary infections, dependence of viral control relied on expression of these innate factors in virally infected cells and not in adaptive immune T cells. Such findings illustrate that functional adaptive responses are less effective in providing protection against reinfections in the absence of innate mechanisms. This demonstrates the importance of intact innate mechanisms when considering effective vaccine strategies.