Animals have played a vital role in every stage of space exploration, from early sub-orbital flights to contemporary missions. New physiological and psychological challenges arise with plans to venture deeper into the solar system. Advances in chimeric and knockout animal models, along with genetic modification techniques have enhanced our ability to study the effects of microgravity in greater detail. However, increased investment in the purposeful design of habitats and payloads, as well as in AI-enhanced behavioral monitoring in orbit can better support the ethical and effective use of animals in deep space research.