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Countering clandestinely delivered nuclear and radiological threats requires a multielement, global, civil/military, system-of-systems approach. One important element is geographically layered, sensor-based detection of threat objects, including radiation detection systems. An effective defense against these threats should take advantage of the latest developments in radiation detection technology. This paper reviews the physics of nuclear detection, and points out areas where improvements can be anticipated, via case studies of technologies such as gamma-ray imaging, advanced radiography, large-area detectors, and active interrogation.