RNA silencing controls numerous developmental processes in eukaryotic organisms from fungi, plants, to animals. In plants as well as in animals, this system of RNA regulation functions as part of an immune response against invading viruses. From transitive RNA silencing to virus-induced gene silencing (VIGS), the systemic effects are proven to be the core of RNA silencing. This article reviews the latest advances in view of the effect of cellular RDR6, an RNA-dependent RNA polymerase (RdRp), on systemic RNA silencing, systemic virus silencing, and discusses the abilities of viral suppressors in modulating RNA silencing efficiency to establish effective infection.