The goals of space exploration are to point toward human missions to the Moon and Mars. Significant scientific and technological challenges must be addressed to support such ambitious goals, including the effects of space factors on biological systems. In long-term missions, the sustainability of human life relies on the development of sustainable closed artificial ecosystems, defined as Bioregenerative Life Support Systems (BLSS). In these systems, higher plants are key organisms for resource regeneration and food production as well as for waste recycling. Furthermore, there is increasing awareness that plant cultivation in space is needed for the development of nutritional countermeasures against physical and psychological stresses faced by the crew. The realization of BLSS requires both advancing knowledge in fundamental plant biology—to identify plants’ adaptive strategies and define crop requirements that can be modified in the harsh space environment—and developing novel agro-technologies to maximize resource use. In this chapter, we discuss the existing knowledge within the context of the new space exploration roadmaps and highlight the potential benefits that improvements in plant space biology and crop science can bring to Earth.