During the past 10-15 years, major advances have been made in understanding the pathophysiologic events that occur following central nervous system insults. It has become clear that a variety of insults have in common their ability to initiate a complex cascade of biochemical events at the cellular level which, over time, lead to neuronal death. Because these events take time to occur, interruption of these cascades offers the hope of specific neuron-salvaging therapy, even when given after the insult, and provides a major step forward from conventional supportive care. This paper reviews these principles as they relate to traumatic brain injury, with emphasis on excitatory amino acid neurotransmitter toxicity (excitotoxicity). Preliminary results in animal experiments and in severely head-injured children are discussed.