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In the post-9/11 world, information technology is an indispensable part of making our nation safer. Critical national security missions in the context of various data and technical domain challenges could benefit from establishing an intelligence and security informatics research discipline. Just as biomedical informatics addresses information management issues in biological and medical applications, ISI would address such issues for intelligence and security applications.The knowledge discovery from databases methodology shows promise in addressing unique ISI challenges. KDD has already proved successful in other information-intensive, knowledge-critical domains including business, engineering, biology, and medicine.This article is part of a special issue on Homeland Security.