The appropriate formation of specific RNA-protein complexes regulates the normal synthesis, trafficking, and metabolism of intracellular RNA. For RNA viruses, these interactions are essential for replication and translation of the viral genome, as well as packaging of progeny strands into mature virions. Sequence-specific RNA-protein interactions allow the replication and translation machinery to distinguish between viral and host-cell RNA species, thus insuring that the viral replicative apparatus acts on the appropriate RNA targets. Identifying these proteins and determining their biological activities provide important clues about the mechanisms of viral replication. Their physiological importance suggests that blocking these interactions may be effective means of inhibiting viral replication. Thus, the identification and characterization of sequence-specific RNA-binding proteins are valuable steps in the development of potent and selective antiviral agents.