MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals, plants, and protozoa. They function posttranscriptionally by base-pairing to the 3′-untranslated regions (3′-UTRs) of target mRNAs, leading to translational repression or mRNA decay. This review discusses the principles of miRNA-mRNA interactions and the proteins that interact with miRNAs to mediate repression. It highlights the multiple and often contradictory mechanisms of miRNA action, including translational repression and mRNA decay, and addresses the cellular localization of miRNA-mediated events. The role of RNA-binding proteins in activating or relieving miRNA repression is also discussed. Key components of miRNA-induced silencing complexes (miRISCs) include Argonaute (AGO) and GW182 family proteins, which are essential for miRNA-mediated repression. The review covers the molecular details of miRNA-mRNA interactions, the involvement of miRISC components, and the mechanisms of translational repression and mRNA decay. It also explores the modulation of miRNA-mediated repression by RNA-binding proteins and the activation of translation by miRNAs under certain conditions.MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in animals, plants, and protozoa. They function posttranscriptionally by base-pairing to the 3′-untranslated regions (3′-UTRs) of target mRNAs, leading to translational repression or mRNA decay. This review discusses the principles of miRNA-mRNA interactions and the proteins that interact with miRNAs to mediate repression. It highlights the multiple and often contradictory mechanisms of miRNA action, including translational repression and mRNA decay, and addresses the cellular localization of miRNA-mediated events. The role of RNA-binding proteins in activating or relieving miRNA repression is also discussed. Key components of miRNA-induced silencing complexes (miRISCs) include Argonaute (AGO) and GW182 family proteins, which are essential for miRNA-mediated repression. The review covers the molecular details of miRNA-mRNA interactions, the involvement of miRISC components, and the mechanisms of translational repression and mRNA decay. It also explores the modulation of miRNA-mediated repression by RNA-binding proteins and the activation of translation by miRNAs under certain conditions.