Microorganisms are ubiquitous and can be found in almost every habitat and ecological niche on Earth. They thrive and survive in a broad spectrum of environments and adapt to rapidly changing external conditions. It is of great interest to investigate how microbes adapt to different extreme environments and with modern human space travel, we added a new extreme environment: outer space. Within the last 50 years, technology has provided tools for transporting microbial life beyond Earth’s protective shield in order to study in situ responses to selected conditions of space. This review will focus on halophilic archaea, as, due to their ability to survive in extremes, they are often considered a model group of organisms to study responses to the harsh conditions associated with space. We discuss ground-based simulations, as well as space experiments, utilizing archaea, examining responses and/or resistance to the effects of microgravity and UV in particular. Several halophilic archaea (e.g., Halorubrum chaoviator) have been exposed to simulated and actual space conditions and their survival has been determined as well as the protective effects of halite shown. Finally, the intriguing potential of archaea to survive on other planets or embedded in a meteorite is postulated.