In recent years, NASA has renewed its focus on manned missions beyond low Earth orbit. These missions will take astronauts to asteroids, the moon, or to Mars. As mission designs become more concrete, it is clear that they will differ from current missions to the International Space Station (ISS) in many ways, including duration, real-time communication with ground, evacuation options, crew rotations, and distance from Earth. These differences will add new challenges to maintaining human health and performance on long-duration exploratory missions (LDEMs). Given the integral nature of teamwork to the success of space missions, differences from current ISS missions will also pose new risk factors to strong team performance over the course of the missions. Factors influencing team performance have previously been identified on past space missions and studies in analogous environments (e.g., submarines, Antarctic research stations). These existing risk factors that affect team performance may be exacerbated on longer space missions in closer quarters, and new risk factors are likely to emerge. Selecting astronauts with the “right stuff” for the new LDEM teams becomes an essential first step in promoting mission success.