Spatially and temporally restricted expression of Hox genes requires multiple mechanisms at both the transcriptional and the post-transcriptional levels. New insight into this precise expression mechanism comes from recent findings of a novel sense–antisense miRNA combination from the bithorax complex of Drosophila melanogaster.1–4 These two miRNAs encoded from the same locus target 3′ untranslated regions of anterior hox genes, Antp, Ubx and abd-A to establish the dominance of posterior hox gene Abd-B in its expression domain. Such double-edge tools, sense–antisense miRNA combinations, also operate at multiple loci in the genome implicating their wider impact on the post-transcriptional gene regulation in eukaryotes. BioEssays 30:1058–1061, 2008. © 2008 Wiley Periodicals, Inc.