The discovery that all living entities express many RNAs beyond mRNAs, tRNAs and rRNAs has been a surprise in the past two decades. In fact, regulatory RNAs (regRNAs) are plentiful, and we report stunning parallels between their mechanisms and functions in prokaryotes and eukaryotes. For instance, prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats) defense systems are functional analogs to eukaryotic RNA interference processes that preserve the cell against foreign nucleic acid elements. Regulatory RNAs shape the genome in many ways: by controlling mobile element transposition in both domains, via regulation of plasmid counts in prokaryotes, or by directing epigenetic modifications of DNA and associated proteins in eukaryotes. RegRNAs control gene expression extensively at transcriptional and post-transcriptional levels, with crucial roles in fine-tuning cell environmental responses, including intercellular interactions. Although the lengths, structures and outcomes of the regRNAs in all life kingdoms are disparate, they act through similar patterns: by guiding effectors to target molecules or by sequestering macromolecules to hamper their functions. In addition, their biogenesis processes have a lot in common. This unifying vision of regRNAs in all living cells from bacteria to humans points to the possibility of fruitful exchanges between fundamental and applied research in both domains.