In Japan, over 5,000 deaths per year are a result of traumatic brain injury (TBI) with most being due to motor vehicle accidents. Survivors of TBI number into the hundreds of thousands and are often left with debilitating neurological deficits. Recently it has been identified that much of the brain damage after TBI develops over time with the primary injury initiating a secondary injury cascade made up of deleterious pathophysiological and biochemical reactions. The delayed development of secondary injury creates an opportunity for therapeutic intervention and considerable effort is being directed toward identifying the secondary injury factors and developing interventions that may potentially prevent their actions. Several secondary injury factors have been identified including oxidative stress, changes in blood flow, neurotransmitters and ionic changes, oedema and energy failure. Of these, Mg(2+) decline has been identified as playing a crucial role in the secondary injury process, in part because of its central role in the regulation of a large number of other known injury factors. This brief review will summarize the experimental evidence supporting a critical role of Mg(2+) in the pathophysiology of TBI, and will examine the use of magnesium salts as a therapeutic intervention.