The stress that the space environment can induce on plant physiology is of both abiotic and biotic nature. The abiotic space environment is characterized by ionizing radiation and altered gravity, geomagnetic field (GMF), pressure, and light conditions. Biotic interactions include both pathogenic and beneficial interactions. Here, we provide an overall picture of the effects of abiotic and biotic space-related factors on plant physiology. The knowledge required for the success of future space missions will lead to a better understanding of fundamental aspects of plant physiological responses, thus providing useful tools for plant breeding and agricultural practices on Earth. The activity of PIN proteins allows the movement of auxin out of the cells and the formation of an asymmetrical gradient of the hormone, that causes the inhibition of cell elongation on the lower side of the root, thereby causing the gravitropic root growth 14 , 15 . Other plant growth regulators play a role in gravitropism, including brassinosteroids 16 , ethylene 17 , gibberellic acid 18 , jasmonic acid 19 , and Ca 2+ signaling 20 . Moreover, phytohormones are hardly mentioned in plant-based studies in space due to technical constraints, like sample storage. In addition to the crop species, the use of plant model systems, for which numerous genetic/molecular resources and tools are available, is facilitating the study of these basic mechanisms and subsequent translational research. The knowledge gained on the control of key traits affecting plant adaptation, survival, and productivity will provide powerful tools for space-targeted precision breeding. X-ray exposure of Brassica rapa to doses up to 30 Gy does not induce detrimental effects on growth, while it stimulates the production of antioxidants, improving plant defence and, concurrently, nutritional value 46 . In Beta vulgaris , ionizing radiation (10 Gy) and specific light quality regimes interact in a complex manner to regulate photosynthesis and the accumulation of bioactive compounds in leaf edible tissues. Optimization of growth, for example, seems more likely than the development of a new sensory modality 85 . Plants respond to atmospheric variations in pressure and composition The development of greenhouses on Mars, on the Moon, and in Earth orbit considers the use of low atmospheric pressures (hypobaria) to address systems and engineering limitations 86 . It is reasonable to expect that reduced-pressure atmospheres will be used to decrease the lift costs of structural components and consumables for future transit vehicles and surface missions. In fact, mass reduction increases the space mission length and launched payloads 87 . However, alterations in atmospheric pressure are known to have effects on the physiology and development of plants 88 . Clarifying the mechanisms behind the physiological adaptation of plants to hypobaria is therefore very relevant to space exploration in the effort to expand food production in orbital and extra-terrestrial controlled agriculture. Growing plants under reduced pressure affects their growth and, depending on the species, may lead to either positive or negative effects. These effects are also correlated to atmospheric O 2 and CO 2 concentrations 89 . Low atmospheric pressure also affects water movement: transpiration rates increase as atmospheric pressure is reduced, even at high relative humidity, influencing stomatal aperture independently of relative humidity 90 . In general, plants show adaptation not only to hypobaria but also to gradients of atmospheric pressure, which induces the activation of genes that code for metabolic processes involved in the hypoxia stress response 88 . Crucially, under microgravity conditions free air convection is restricted, limit heat and gas distribution, causing unfavorable conditions close to the leaf. While uptake of NH 4 + and NO 3 − were improved by 30 kPa hypobaria under the same O 2 partial pressure 101 , low oxygen stress induces the production of lettuce protective phytochemicals and the free This important result underlines the importance of evaluating the biological consequences of hypobaric environments for the exploration of life-support habitats. Our overall understanding of how atmospheric pressure influences plants and, hence, directly plant-driven bioregenerative fluxes is still very limited, and studies of the underlying genetic/molecular mechanisms are much needed 89 . Other environmental factors, such as humidity and atmospheric temperature and composition (including volatile organic compounds, or VOCs, airborne contaminants, and dust), which could crosstalk with the hypobaria response, are also very important and could affect plant growth in planetary greenhouses. Beneficial microbes, especially endophytes, significantly increase host fitness through improved nutrition and protection from biotic and abiotic stress 122 , 125 . Photosynthetic microorganisms may contribute to plant growth with their potential biostimulant effects for life in closed environments, as recently reviewed 126 . On the other hand, plant-microbe associations can contribute to supporting plants survival, growth, and health under harsh environmental conditions such as those of space missions. Understanding the plant responses to atmospheric pressure variations, like hypobaria, is very relevant to space exploration in the effort to expand food production in orbital and extra-terrestrial controlled agriculture. Light influences plant growth, from seed germination to flowering and fruiting. The effect of light quality and quantity can help restore meristematic competence under microgravity conditions, and light-emitting diodes (LEDs) are currently used in space farming to modulate spectral composition for optimal plant growth. Plant-microbe associations can contribute to support plants survival, growth and health under harsh environmental conditions such as those of space missions.