Addressing the behavioral health needs of astronauts clearly requires collaborations involving researchers, clinicians and operational support personnel, program administrators, and the astronauts themselves. However, such collaborations are often compromised by a failure to understand the needs, priorities, constraints, and preferences of potential collaborators. This failure, in turn, can lead to research of poor quality, implementation of programs and procedures that are not evidence-based, and an increased risk of morbidity and mission failure. The experiences of social marketing strategies in health promotion and disease prevention, cultural exchange between developers of evidence-based treatments and consumers, and dissemination and implementation of evidence-based practices in mental health services offer three different models of research-operational collaboration with relevance to behavioral health in space. Central to each of these models are the patterns of interpersonal relations and the individual, social, and organizational characteristics that influence these patterns. Any program or countermeasure for behavioral health in space must be both needs-based and evidence-based. The successful development, dissemination, implementation, and sustainability of such a program require communication, collaboration, and consensus among all key stakeholders. To accomplish this, all stakeholders must participate in creating a culture of operational research.