Genome expression profiling has led to the important realization that RNA molecules are more numerous and diverse than previously expected. One aspect of RNA biology that is just beginning to be fully appreciated is the extent to which mRNAs are transported to specific subcellular destinations before being translated, an exquisite mechanism for targeting proteins where they are required in the cell. While several excellent reviews have discussed the subject of mRNA localization, it is only in recent years that high-throughput technologies have been applied to address issues such as the extent and diversity of RNA localization events and mechanisms. This review focuses on these recent functional genomic approaches, their implications, and the new tools and methods that will be needed to further elucidate mRNA localization pathways.