In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) regulate important processes that include mRNA inactivation, viral defense, chromatin modification, and transposon silencing. Recently, nucleolus-associated Cajal bodies in plants have been implicated as sites of siRNA and miRNA biogenesis, whereas in animals siRNA and miRNA dicing occurs in the cytoplasm. The plant nucleolus also contains proteins of the nonsense-mediated mRNA decay pathway that in animals are found associated with cytoplasmic processing bodies (P-bodies). P-bodies also function in the degradation of mRNAs subjected to miRNA and siRNA targeting. Collectively, these observations suggest interesting variations in the way siRNAs and miRNAs can accomplish their similar functions in plants and animals.