The majority of viruses infecting animals and plants today are RNA viruses [1]. There are double-stranded (ds) RNA viruses with dsRNA genomes, as well as (+) and (−)RNA viruses whose genomes are single-stranded (ss) RNA of either positive or negative polarity. RNA viruses have small genomes that rarely exceed 30 kb in size, and a large portion of their genomes is used to encode proteins involved in viral RNA replication. Viral RNA synthesis is catalyzed by the virally encoded RNA-dependent RNA polymerase (RdRp), which lacks any proofreading activity. Although the details of RNA replication greatly vary among viruses, common principles clearly exist in the organization of the replication machinery of different RNA viruses.