Traumatic injury to the central nervous system (CNS) initiates an autodestructive cascade of biochemical and pathophysiological changes that ultimately results in irreversible tissue damage. Known as secondary injury, this delayed injury process is multifactorial in nature and it is generally thought that the simultaneous attenuation of a number of the secondary injury factors will be required for interventional therapies to have a significant beneficial effect on outcome. This review summarizes the growing body of evidence that suggests that magnesium plays a pivotal role in the secondary injury process following CNS trauma, affecting a number of secondary injury factors including neurotransmitter release and activity, ion changes, oxidative stress, protein synthesis, and energy metabolism. By having effects on such a range of secondary injury factors following trauma, pharmacological studies have shown that magnesium may be an effective therapy following neurotrauma, improving survival, motor outcome and alleviating cognitive deficits.