Homology-dependent gene silencing (HdGS) which is the generic term for transcriptional gene silencing (TGS), post-transcriptional gene silencing (PTGS) and RNA-mediated virus-resistance (RmVR) has been shown to frequently occur in transgenic plants. The role of RNA as a target and initiator of PTGS and RmVR is more and more manifested. Because TGS is assumed to be induced by a DNA-DNA interaction-mediated promoter methylation, a possible involvement of RNA in TGS was not really considered up to now. In this review we attempt to demonstrate that all three types of HdGS could be triggered by one RNA-based mechanism. A model proposing TGS as a consequence of RNA-directed DNA methylation (RdDM) and a refined mRNA threshold mechanism are presented. In contrast to the view that high amounts of mRNA are required we assume that the concentration of RNAs that can serve as efficient templates for a plant-encoded RNA-directed RNA polymerase (RdRP) plays a key role in HdGS and possibly also in natural gene regulation of non-transformed cells. According to this idea a particular information must be encoded to render mRNA turn-over products a suitable RdRP substrate. It will be discussed that such a mechanism could account for the silencing phenomena of poorly transcribed transgenes. Finally, an explanation for the coherency between PTGS and DNA methylation is documented.