'RNA silencing' is a highly conserved mechanism leading to suppression of gene expression through nucleotide sequence-specific interactions that are mediated by 21-24 nucleotide-long RNAs. This process was first discovered as an unexpected consequence of transgenesis in plants, and similarly, it was subsequently identified in animals as an anomaly of antisense gene inhibition. We summarize the progressive steps that paved the way to our current understanding of the molecular basis and fundamental biological roles of RNA silencing in both plants and animals. In particular, we describe the general antiviral function of this mechanism in higher plants where it forms the basis of a highly elaborate immune system. All defense systems show some level of fallibility, and RNA silencing is no exception to this rule, as plant viruses have developed sophisticated ways to counteract various steps of the process. Recent work indicates that viruses are also engaged into a similar arms race in insects, but it remains unclear if RNA silencing plays a defensive role against virus infection of higher vertebrates. We also discuss some biotechnological applications of RNA silencing in mammalian cells that have fueled optimism that this mechanism may hold a promising future in antiviral human therapy.