Nerve agents are rapidly acting chemical compounds that can cause respiratory arrest within minutes of absorption. Their speed of action imposes a need for rapid and appropriate reaction by exposed soldiers and others that must administer antidotes quickly enough to save lives. However, a medical defense against nerve agents that depends completely on postexposure antidote treatment has limitations. Because of these limitations military physicians have focused on the possibility of protecting soldiers by medical prophylaxis, or pretreatment, designed to limit the toxicity of a subsequent nerve agent exposure. The inadequacy of postexposure therapy for nerve agent casualties, particularly those with potentially lethal exposures to soman, has been of great concern. Development of pyridostigmine as a nerve agent pretreatment adjunct has substantially improved the ability of the military to protect its soldiers from the lethal effects of nerve agents. A major deficiency of this pretreatment program -- that it does not protect the central nervous system against nerve agent-induced injury -- may be overcome by postexposure administration of anticonvulsants. While centrally acting pretreatments offer more effective protection than does pyridostigmine, their development is limited because of their potential for impairing soldier performance. New research may provide a revolutionary advance in protection against nerve agents with biotechnologically derived pretreatments that bind or inactivate nerve agents in the circulation. 66 references