The risk assessment process is a critical function for military Deployment Toxicology research objectives, emphasizing improved health protection of deployed forces. Reliable risk assessment methodology is essential for decision making related to risk reduction procedures during combat deployment, as well as during routine occupational activities. Such decision making must be based upon quality science that both guides sound judgments in risk characterization and management, and provides necessary health protection tools. The health and fitness of deployed forces must be considered for both acute and long-term issues. Exposure assessment specifies populations that might be exposed to injurious agents, identifies routes of exposure, and estimates the magnitude, duration, and timing of the doses that personnel may receive as a result of their exposure. Acute or short-term catastrophic risks for deployed forces are of immediate concern and must be addressed on a risk prioritization basis using Operational Risk Management (ORM) procedures. However, long-term effects of exposure to the same agents must be considered as part of the overall health concerns for deployed forces. In response to these needs, a number of military, federal government, academic and private sector organizations are currently developing new classes of biologically-based biosensors with the programmed capacity to detect the presence of virtually any environmental chemical or biological stressor with the capacity to induce health consequences in deployed personnel. A major objective of this engineering effort is development of biosensor systems that detect novel (previously unresearched) chemical or biological agents that might be used during international combat or terrorist attacks to induce acute or long-term health effects on military or civilian populations. A large portion of the discussion in this paper is devoted to describing the development, testing, and implementation of tissue-based biosensors (TBBs) that utilize small samples of living tissue from laboratory small animals for a wide range of human risk assessment applications.