Food and nutrition are critical to health and performance and therefore the success of human space exploration. However, the shelf-stable food system currently in use on the International Space Station is not sustainable as missions become longer and further from Earth, even with modification for mass and water efficiencies. Here, we provide a potential approach toward sustainability with the phased addition of bioregenerative foods over the course of NASA’s current mission plans. Significant advances in both knowledge and technology are still needed to inform nutrition, acceptability, safety, reliability, and resource and integration trades between bioregenerative and other food systems. Sustainability goals on Earth are driving similar research into bioregenerative solutions with the potential for infusion across spaceflight and Earth research that benefits both.