Calcium is a major regulator of cell function, acting as a second messenger to relay signals from the cell surface to other parts of the cell. It plays an integral role in contraction of muscle cells and it regulates cell growth and proliferation, as well as cell death (1). The present review will discuss how Ca²+ mediates these functions through the regulation of gene expression. This can be accomplished by Ca²⁺-sensitive protein kinases as well as phosphatases which activate transcription factors. It can also be mediated by direct interaction of Ca²⁺-sensitive proteins with regulatory elements within the DNA sequence itself. Special attention will be given to recent advances in research in the down-stream regulatory element (DRE) and its Ca²⁺-sensitive modulator DREAM (downstream regulatory element antagonist modulator; also named calsenilin or K⁺ channel interacting protein 3 (KChIP3)) (2).