Plant viruses are known for their devastating impact on global agriculture. These intracellular biotrophic pathogens can infect a wide variety of plant hosts all over the world. The synergistic association of plant viruses makes the situation more alarming. It usually promotes the replication, movement, and transmission of either or both the coexisting synergistic viral partners. Although plants elicit a robust antiviral immune reaction, including gene silencing, to limit these infamous invaders, viruses counter it by encoding viral suppressors of RNA silencing (VSRs). Growing evidence also suggests that VSRs play a driving role in mediating the plant viral synergism. This review briefly discusses the evil impacts of mixed infections, especially synergism, and then comprehensively describes the emerging roles of VSRs in mediating the synergistic association of plant viruses.