Polarization of the microtubule cytoskeleton during early oogenesis is required to specify the posterior of the Drosophila oocyte, which is essential for asymmetric mRNA localization during mid-oogenesis and for embryonic axis specification. The posterior determinant oskar mRNA is translationally silent until mid-oogenesis. We show that mutations in armitage and three components of the RNAi pathway disrupt oskar mRNA translational silencing, polarization of the microtubule cytoskeleton, and posterior localization of oskar mRNA. armitage encodes a homolog of SDE3, a presumptive RNA helicase involved in posttranscriptional gene silencing (RNAi) in Arabidopsis, and is required for RNAi in Drosophila ovaries. Armitage forms an asymmetric network associated with the polarized microtubule cytoskeleton and is concentrated with translationally silent oskar mRNA in the oocyte. We conclude that RNA silencing is essential for establishment of the cytoskeletal polarity that initiates embryonic axis specification and for translational control of oskar mRNA.