Control of gene expression by Ca2+ is a well known phenomenon acting through three major pathways: (i) changes in the transactivating properties of transcription factors after induction of Ca2+-dependent kinases and phosphatases (ii) Ca2+-dependent interaction between calmodulin and S-100 proteins with basic helix-loop-helix (bHLH) transcription factors that prevents binding to DNA and (iii) direct interaction between Ca2+-free DREAM and DNA that represses transcription. Because the first mechanism has been extensively reviewed, (Gallin, W. J., Greenberg, M. E. (1995). Calcium regulation of gene expression in neurons: the mode of entry matters. Curr Opin Neurobiol 5: 367-374; Santella, L., Carafoli, E. (1997). Calcium signaling in the cell nucleus. FASEB J, 11: 1091-1109) this commentary will focus on the other two with special emphasis on DREAM, the first EF-hand protein known to specifically bind DNA and regulate transcription in a Ca2+-dependent manner (Carrion, A. M.; Link, W. A., Ledo, F., Mellstrom, B., Naranjo, J. R. (1999). DREAM is a Ca2+-regulated transcriptional repressor, Nature. 398: 80-84).