Riboswitches are regulatory motifs found in the UTRs of mRNAs that bind cellular ligands and typically block mRNA expression by forming transcription termination stem loops. The identity of primary ligands for several candidate riboswitches has remained elusive, but a study now reveals that the ydaO riboswitch, which is widespread in bacteria, selectively responds to the second messenger cyclic di-AMP (c-di-AMP). Previous work suggested that ydaO senses ATP; however, Nelson et al. found that the binding affinity of c-di-AMP was more than six orders of magnitude greater than that of ATP.Furthermore,c-di-AMP was shown to trigger transcription termination in vitro, and this observation was supported by in vivo experiments. This is the first riboswitch that has been shown to respond to c-di-AMP and its identification greatly increases the number of genes known to be regulated by this important second messenger.