Active resistance to viruses is afforded by plant disease resistance (R) genes, which encode proteins with nucleotide-binding (NB) and leucine-rich repeat (LRR) domains. Upon recognition of pathogen-derived elicitors, these NB–LRR proteins are thought to initiate a number of signaling pathways that lead to pathogen restriction. However, little is known about the molecular mechanisms that ultimately curtail virus accumulation. Here, we show that the co-expression of a plant NB–LRR protein with its cognate elicitor results in an antiviral response that inhibits the translation of virus-encoded proteins inNicotiana benthamiana. This antiviral response is dependent on viralciselements, and, upon activation of the NB–LRR protein, viral transcripts accumulate but do not associate with ribosomes. The induced inhibition of viral transcript translation and NB–LRR-mediated virus resistance were compromised by the downregulation ofArgonaute4-like genes. Argonaute proteins have been implicated in small RNA-mediated RNA degradation, and in degradation-independent translational control. Our results suggest that the engagement of Argonaute proteins in the specific translational control of viral transcripts is a key factor in virus resistance mediated by NB–LRR proteins.