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This article provides an overview of the technical challenges and solutions for ISP designers for strategic inertial navigation systems (INSs). The design descriptions herein are mostly generic, with occasional references to existing or past strategic systems. The article discusses four primary topics, namely, system design options, environments and mitigation techniques, preflight calibration and alignment (C&A) in-flight navigation mechanizations, and test and verification. IEEE standard terminology of inertial sensors and inertial systems is used throughout the article. The best-known application of ISPs is stabilization and control of payloads such as electro-optical sensors and laser beams. Perhaps less well known is that ISPs are used in a variety of aircraft and missile navigation systems. With the introduction of digital computers, the breadth of application of ISPs for navigation began to diminish, and strapdown INS became prevalent. This trend has accelerated with the navigation aiding of the global positioning system (GPS), which can render a strapdown inertial measurement unit (IMU) more accurate than the best ISPs. Today, only self-contained precision navigation systems use ISPs. Strategic navigation systems are among this small group.