Long-duration space missions (LDMs) place unique demands on humans that can affect their adaptability to live and work in space. A study was conducted to identify the demands and critical skills needed to successfully cope with LDMs. Based on research and experiences in space and analogous environments, questionnaires were developed and administered to LDM experts who rated the criticality of non-technical mission demands and relevant astronaut skills. Findings revealed a group of critical proficiencies in which the level of criticality for LDM is different from short duration missions (SDMs). For example, specific proficiencies in the teamwork and group living categories assume greater importance during LDMs. These critical skills and job demands must be accounted for in upgrades to the tools and procedures used in the selection, training, and support of LDM astronauts.