Magnesium is an essential mineral that is needed for a broad variety of physiological functions. The usual daily magnesium uptake with a western diet is sufficient to avoid deficiency but seems not to be high enough to establish high normal serum magnesium concentrations that are protective against various diseases. Changes in magnesium homeostasis mainly concern the extracellular space, as the intracellular magnesium concentration is well regulated and conserved. The extracellular magnesium concentration is primarily regulated by the kidney, the mechanisms of this regulation have been elucidated recently. Due to the growing knowledge about the regulation of extra- and intracellular magnesium concentrations and the effects of changed extracellular magnesium levels the use of magnesium in therapy gains more widespread attention.