Future space missions will involve multi-national crews of men and women who will perform complicated tasks over long periods of time. Under these conditions, social and cultural factors will play a significant role in influencing crew morale, cohesiveness, and performance. Important socio-cultural issues include language differences between crew members, cultural and racial biases, gender stereotyping, and differences in career motivation. Negative aspects of these issues include the scapegoating and isolation of individuals who are seen as different from the rest of the crew; the formation of subgroups, which creates divisiveness and unhealthy competition; the presence of interpersonal tension, which leads to decreased cohesiveness and increased withdrawal and territorial behavior; and the displacement of tension and anger to colleagues and families on Earth, which leads to poor crew-ground communications. The negative impact of these socio-cultural factors can be minimized by paying attention to issues of compatibility during crew selection, by pre-flight training and sensitization to these issues, by in-flight monitoring and support from the ground, and by post-flight debriefings that help space travelers deal with the sequelae of problems that might have emerged during the mission.