Post‐transcriptional gene‐silencing (PTGS) was first discovered in plants and results from the sequence‐specific degradation of RNA. Degradation can be activated by introducing transgenes, RNA viruses or DNA sequences that are homologous to expressed genes. A similar RNA degradation mechanism which is inducible by double‐stranded RNA (dsRNAs), has been discovered recently in vertebrates, invertebrates and protozoa. dsRNAs may also be potent activators of PTGS in plants. PTGS is not cell autonomous, suggesting the synthesis of sequence‐specific silencing signals which are not only moving through the plant but are also amplified and an RNA‐directed RNA Polymerase which has recently been cloned from various plant species is a candidate enzyme for amplifying silencing signals. The natural role of PTGS seems to be as a defence against plant viruses, so what first appeared to be RNAs on the attack may now be considered RNAs on the defense. BioEssays 22:520–531, 2000. © 2000 John Wiley & Sons, Inc.