A greater awareness of and increased interest in the use of modeling and simulation (M&S) has been demonstrated at many levels within the Department of Defense (DoD) and all the Armed Services agencies in recent years. M&S application is regarded as a viable means of lowering the life cycle costs of theater missile defense (TMD) weapon system acquisition beginning with studies of new concepts of warfighting through user training and post-deployment support. The Missile Research, Engineering, and Development Center (MRDEC) of the U.S. Army Aviation and Missile Command (AMCOM) has an extensive history of applying all types of M&S to TMD weapon system development and has been a particularly strong advocate of hardware-in-the-loop (HWIL) simulation for many years. Over the past 10 years MRDEC has developed specific and dedicated HWIL capabilities for TMD applications in both the infrared and radio frequency sensor domains. This paper provides an overview of the infrared-based TMD HWIL missile facility known as the Imaging Infrared System Simulation (I2RSS) which is used to support the Theater High Altitude Air Defense (THAAD) missile system. This facility uses M&S to conduct daily THAAD HWIL missile simulations to support flight tests, missile/system development, independent verification and validation of weapon system embedded software and simulations, and missile/system performance against current and future threat environments. This paper describes the THAAD TMD HWIL role, process, major components, HWIL verification/validation, and daily HWIL support areas in terms of both missile and complete system.