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Human performance, particularly that of the warfighter, has been the subject of a large amount of research during the past few decades. For example, in the Medline database of medical and psychological research, 1,061 papers had been published on the topic of “military performance” as of October 2003. Because warfighters are often pushed to physiological and mental extremes, a study of their performance provides a unique glimpse of the interplay of a wide variety of intrinsic and extrinsic factors on the functioning of the human brain and body. Unfortunately, it has proven very difficult to build performance models that can adequately incorporate the myriad of physiological, medical, social, and cognitive factors that influence behavior in extreme conditions. The chief purpose of this chapter is to provide a neurobiological (neurochemical) framework for building and integrating warfighter performance models in the physiological, medical, social, and cognitive areas. This framework should be relevant to all other professionals who routinely operate in extreme environments. The secondary purpose of this chapter is to recommend various performance metrics that can be linked to specific neurochemical states and can accordingly strengthen and extend the scope of the neurochemical model.