In the couse of evolution, calcium has emerged as the most versatile intracellular messenger. Its concentration within cells is controlled by reversible binding to specific protein acting as sensors to decode its information. The decoding operation is based on specific conformational changes in these sensor proteins. Other proteins intrinsic to membranes (plasma membrane, endosarcoplasmic reticulum, mitochondria, nuclear envelope) simply control calcium concentration by transporting it across membrane boundaries. Calcium is an ambivalent signaling agent. It carries information to all processes important to cell life, including excitation-contraction coupling, secretion, gene transcription and enzyme activity through protein phosphorylation-dephosphorylation. However, it also transmits signals that promote programmed demise of cells and, when escaping control, it may also precipitate toxic cell death.