A balance of magnesium is vital to the well-being of all organisms. Magnesium is a relatively abundant ion in Earth's crust and mantle and is highly bioavailable in the hydrosphere. This availability, in combination with a useful and very unusual chemistry, may have led to its utilization in evolution as an ion for signaling, enzyme activation, and catalysis. However, the unusual nature of ionic magnesium has also led to a major challenge in the use of the ion in biological systems. Biological membranes are impermeable to magnesium (and other ions), so transport proteins must facilitate the flow of magnesium, both into and out of cells and intracellular compartments.