The article discusses the growing class of RNA interference (RNAi) therapeutics, which have been approved by the U.S. Food and Drug Administration (FDA) to treat various diseases by controlling target gene expression at the posttranscriptional level. Currently, six RNAi-based therapeutics are FDA-approved, with five of them acting on the 3' untranslated regions (3'UTRs) of target mRNAs, similar to the mechanism of action of microRNAs (miRNAs). Three of these therapeutics induce target mRNA degradation or cleavage via near-complete rather than complete base-pair complementarity. The authors highlight the common and unique chemistry and molecular pharmacology of these therapeutics, emphasizing the need for a unified nomenclature to align with current pharmacological criteria based on the mechanism of action. They argue that the term "RNAi therapeutics" should be used to encompass all forms of RNAi molecules, including siRNAs and miRNAs, to provide a clear and comprehensive classification. The article also reviews the clinical applications and mechanisms of action of the six FDA-approved siRNA therapeutics, including their chemical modifications, delivery methods, and therapeutic targets.The article discusses the growing class of RNA interference (RNAi) therapeutics, which have been approved by the U.S. Food and Drug Administration (FDA) to treat various diseases by controlling target gene expression at the posttranscriptional level. Currently, six RNAi-based therapeutics are FDA-approved, with five of them acting on the 3' untranslated regions (3'UTRs) of target mRNAs, similar to the mechanism of action of microRNAs (miRNAs). Three of these therapeutics induce target mRNA degradation or cleavage via near-complete rather than complete base-pair complementarity. The authors highlight the common and unique chemistry and molecular pharmacology of these therapeutics, emphasizing the need for a unified nomenclature to align with current pharmacological criteria based on the mechanism of action. They argue that the term "RNAi therapeutics" should be used to encompass all forms of RNAi molecules, including siRNAs and miRNAs, to provide a clear and comprehensive classification. The article also reviews the clinical applications and mechanisms of action of the six FDA-approved siRNA therapeutics, including their chemical modifications, delivery methods, and therapeutic targets.