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As astronauts venture farther from Earth, and stay for longer periods, the space food system will increase in importance. Crop production can supplement a pre-packaged space diet to provide nutrition and dietary variety for space crews. In future missions, bioregenerative approaches may be used to generate a larger percentage of the diet, as well as help to reduce life support system burdens and resupply from Earth. Plants may also provide behavioral health benefits to crew members living in the isolated, confined environment of a space habitat. A number of unique challenges exist for growth of plants in microgravity and on other reduced gravity surfaces like the moon and Mars. Testing plant growth inside the Veggie and Advanced Plant Habitat (APH) chambers on the International Space Station is allowing us to understand the impacts of gravity and spaceflight on crop growth, nutritional content, acceptability, and the importance of plants to astronauts living and working away from Earth. We are also gaining a better understanding of food safety concerns and the behavior of space plant microbiomes and plant pathogens, but major gaps in knowledge remain. As we move from research towards operational space crop production to enable exploration, there are numerous gaps in technology, knowledge, and practice related to space crop growth that must be addressed. Research and development in key focus areas such as effective water and nutrient delivery at variable gravity levels, autonomous plant health monitoring, growth system cleaning and disinfection, and selection of ideal space crops are needed to fill these gaps. Breeding or engineering custom space crops may impact areas including plant growth and development, plant physiology, produce nutrition, organoleptic acceptability, and post-harvest characteristics, and these may further enable space crop production scenarios. Space crop challenges are multifaceted and require diverse interdisciplinary teams working together to develop effective solutions. Solving these requires an array of skill sets from across the biological and physical sciences, engineering, and human social sciences. Solutions to help ensure food security off-Earth may also translate to more sustainable terrestrial crop production approaches, and regular dialog between industry, academia, and government organizations working in related fields benefit all. Additional help can come from engagement with student researchers at various levels through courses, participatory science projects, and open science activities which can provide useful data. Global coordination and integration between space agencies and partners will be essential.