Cells have complex membranous organelles for the compartmentalization and regulation of most intracellular processes. Organelle biogenesis and maintenance requires newly synthesized proteins, each of which needs to go from the ribosome translating its mRNA to the correct membrane for insertion or translocation to an organellar subcompartment. Decades of research have revealed how proteins are targeted to the correct organelle and translocated across one or more organelle membranes to the compartment where they function. The paradigm examples involve interactions between a peptide sequence in the protein, localization factors, and various membrane-embedded translocation machineries. Membrane translocation is either cotranslational or posttranslational depending on the protein and target organelle. Meanwhile, research in embryos, neurons and yeast revealed an alternative targeting mechanism in which the mRNA is localized and only then translated to synthesize the protein in the correct location. In these cases, the targeting information is encoded by cis-acting sequences in the mRNA (“Zipcodes”) that interact with localization factors and, in many cases, are transported by molecular motors on cytoskeletal filaments. Recently, evidence has been found for this “mRNA-based” mechanism in organelle protein targeting to endoplasmic reticulum, mitochondria, and the photosynthetic membranes within chloroplasts. Here we review known and potential roles of mRNA localization in protein targeting to and within organelles. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. ► mRNA distribution in cellular systems is essential for cellular function. ► mRNA and protein elements are signals for the differential distribution. ► Multiple modes for the association of mRNAs with membranes exist. ► mRNA localization is one important way for regulation of protein translocation.