Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, Alan Faden and Steven Salzman discuss the pharmacological approaches that have the most experimental support. These include corticosteroids, antioxidants and free-radical scavengers, modulators of arachidonate metabolism, gangliosides, monoamine modulators, opioid receptor antagonists, TRH and its analogs, NMDA receptor antagonists, Ca2+ channel antagonists and platelet-activating factor antagonists.