RNA silencing occurs in a wide variety of organisms, including protozoa, fungi, plants and animals and involves recognition of a target RNA and initiation of a sequence-specific RNA degradation pathway in the cytoplasm. In the last few years, there have been considerable advances in our understanding of post-transcriptional gene silencing (PTGS). This mechanism is conceived as a natural antiviral defense system in plants that is activated as a response to double-stranded RNA (dsRNA) formed during virus replication. To develop new approaches for plant protection against virus diseases based on PTGS we have expanded previous findings on RNA interference (RNAi) in animals by using dsRNA to specifically interfere with virus infection in plants. This approach differs from strategies based on transgenic expression of RNAs but still relies on PTGS as a means to achieve pathogen-derived resistance (PDR). Our findings suggest that exogenously supplied dsRNA could form the basis for the development of an environmentally safe, new biotechnological tool aimed at protecting crops against virus diseases, provided that some limitations of the current status of the approach could be overcome.