The body axes of the fruit fly are established in mid-oogenesis by the localization of three mRNA determinants, bicoid, oskar, and gurken, within the oocyte. General mechanisms of RNA localization and cell polarization, applicable to many cell types, have emerged from investigation of these determinants in Drosophila oogenesis. Localization of these RNAs is dependent on the germline microtubules, which reorganize to form a polarized array at mid-oogenesis in response to a signaling relay between the oocyte and the surrounding somatic follicle cells. Here we describe what is known about this microtubule reorganization and the signaling relay that triggers it. Recent studies have identified a number of ubiquitous RNA binding proteins essential for this process. So far, no targets for any of these proteins have been identified, and future work will be needed to illuminate how they function to reorganize microtubes and whether similar mechanisms also exist in other cell types. Developmental Dynamics 235:1455–1468, 2006. © 2006 Wiley-Liss, Inc.