Antiviral defense is one of the important roles of RNA silencing in plants. Virus-derived small interfering RNAs (vsiRNAs) are found in the infected host cells, indicating that the host RNA silencing machinery can target viral RNAs for destruction. With the development of high-throughput sequencing of vsiRNAs, recent genetic studies have shed light on the origin and composition of vsiRNAs and their potential functions in the regulation of gene expression. Here, we briefly describe the origin and biogenesis of vsiRNAs, and review the recent discoveries regarding vsiRNA-mediated RNA silencing of viral genomes and host transcripts. This will better our understanding of virus pathogenicity and RNA silencing-related host-pathogen interactions in plants.