The Epstein-Barr virus (EBV) SM protein is a member of a highly conserved family of proteins present in most mammalian herpes viruses. There is a significant amount of functional and sequence divergence among the homologs encoded by the human herpes viruses, including differences in mechanism of action and varying effects on splicing and transcription. Nevertheless, in those cases where it has been studied, these proteins are essential for lytic replication of the virus. The mechanism by which SM regulates gene expression operates at the level of mRNA stability, processing, and export. SM enhances expression of EBV lytic genes and has both positive and negative effects on cellular gene expression. In addition to enhancing accumulation of EBV gene mRNAs, SM has important effects on cellular mRNAs, altering the host cell gene expression profile to facilitate viral replication. This article describes the current state of knowledge regarding the role of EBV SM in cellular and viral gene regulation and summarizes some of the similarities and differences with the ORF57 homolog from Kaposi's sarcoma-associated herpes virus (KSHV/HHV8).