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The animal habitat under development for the International Space Station (ISS) provides a unique opportunity for the physiological and biological science community to perform controlled experiments in microgravity on rats and mice. This paper discusses the complexities that arise in developing a new animal habitat to be flown aboard the ISS. Such development is incremental and moves forward by employing the past successes, learning from experienced shortcomings, and utilizing the latest technologies. The standard vivarium cage on the ground can be a very simple construction, however the habitat required for rodents in microgravity on the ISS is extremely complex. This discussion presents an overview of the system requirements and focuses on the unique scientific and engineering considerations in the development of the controlled animal habitat parameters. In addition, the challenges to development, specific science, animal welfare, and engineering issues are covered.