Ca²⁺ is a universal second messenger used to regulate a wide range of cellular processes such as fertilization, proliferation, contraction, secretion, learning and memory. Cells derive signal Ca²⁺ from both internal and external sources. The Ca²⁺ flowing through these channels constitute the elementary events of Ca²⁺ signalling. Ca²⁺ can act within milliseconds in highly localized regions or it can act much more slowly as a global wave that spreads the signal throughout the cell. Various pumps and exchangers are responsible for returning the elevated levels of Ca²⁺ back to the resting state. The mitochondrion also plays a critical role in that it helps the recovery process by taking Ca²⁺ up from the cytoplasm. Alterations in the ebb and flow of Ca²⁺ through the mitochondria can lead to cell death. A good example of the complexity of Ca²⁺ signalling is its role in regulating cell proliferation, such as the activation of lymphocytes. The Ca²⁺ signal needs to be present for over two hours and this prolonged period of signalling depends upon the entry of external Ca²⁺ through a process of capacitative Ca²⁺ entry. The Ca²⁺ signal stimulates gene transcription and thus initiates the cell cycle processes that culminate in cell division.