Rhizobia-derived nodulation factors initiate a spike in calcium levels in the nucleus of plant root cells, which leads to the activation of symbiosis-associated genes and root nodule organogenesis. Nuclear calcium- and calmodulin-dependent kinase (CCaMK) has emerged as a key regulator in symbiotic development, but the underlying mechanism has been unclear. Singh et al. now report that increased calcium levels induce the CCaMK-mediated site-specific phosphorylation of its interaction partner CYCLOPS, which results in the dissociation of CYCLOPS from the complex and the release of its DNA-binding and transcriptional activation domains. The authors show that CYCLOPS binds to a specific motif in the promoter of NODULE INCEPTION (NIN; a mediator of organogenesis) to induce gene expression. These data reveal a mechanism whereby CCaMK 'decodes' a symbiotically induced calcium signal to initiate symbiotic organ development.