Bioterrorism is no longer a hypothetical construct but a reality. Nevertheless, disease detection and intervention currently remain largely reliant on clinical assessment. Technology providing early detection of disease could impact the care of individual patients and the evolution of epidemic spread. Hyperspectral Imaging (HSI) is a remote sensing technology developed originally by the Department of Defense that combines high-resolution imaging with chemical spectroscopy. In other medical applications HSI is emerging as a new means of early or more sensitive detection of changes in tissue that can be used to define pathology, predict clinical outcomes and adapt therapy. As a small, robust, camera based, non-invasive device, HSI may be well suited to aid in defense against biological warfare or epidemic disease by providing early detection or confirmation of disease and by monitoring the efficacy of vaccination or therapy. Crossover applications exist in the evaluation and treatment of emerging diseases. HSI is well suited to be a screening tool to provide earlier or more accurate detection of disease in an at risk population to better treat and contain disease.