Spaceflight has received renewed interest in recent years. With the increase in commercial and private space travel opportunities through companies like SpaceX and Axiom Space, and a planned return to the moon by NASA, understanding the human side of spaceflight is salient to even casual fans of space. Human factors researchers and engineers have continued to address challenging questions of how to ensure humans survive and thrive in a hostile environment, and how to achieve complex mission objectives beyond low Earth orbit. The articles in this special issue capture cutting edge research that will enable humans to achieve the next steps on the journey to the moon and Mars.