Mg2+ is an essential mineral with pleotropic impacts on cellular physiology and functions. It acts as a cofactor of several important enzymes, as a regulator of ion channels such as voltage-dependent Ca2+ channels and K+ channels and on Ca2+-binding proteins. In general, Mg2+ is considered as the main intracellular antagonist of Ca2+, which is an essential secondary messenger initiating or regulating a great number of cellular functions. This review examines the effects of Mg2+ on mitochondrial functions with a particular focus on energy metabolism, mitochondrial Ca2+ handling, and apoptosis.