Long-duration missions bring numerous risks that must be understood and mitigated in order to keep astronauts healthy, rather than treat a diagnosed health disorder. Having a limited medical support from mission control center on space exploration missions, crew members need a personal health-tracking tool to predict and assess his/her health risks if no preventive measures are taken. This paper refines a concept employing technologies from Prognostics and Health Management (PHM) for systems, namely real-time health monitoring and condition-based health maintenance with predictive diagnostics capabilities. Mapping particular PHM-based solutions to some Human Health and Performance (HH&P) technology candidates, namely by NASA designation, the Autonomous Medical Decision technology and the Integrated Biomedical Informatics technology, this conceptual paper emphasize key points that make the concept different from that of both current conventional medicine and telemedicine including space medicine. The primary benefit of the technologies development for the HH&P domain is the ability to successfully achieve affordable human space missions to Low Earth Orbit (LEO) and beyond. Space missions on the International Space Station (ISS) program directly contribute to the knowledge base and advancements in the HH&P domain, thanks to continued operations on the ISS, a unique human-tended test platform and the only test bed within the space environment. The concept is to be validated on the ISS, the only “test bed” on which to prepare for future manned exploration missions. The paper authors believe that early self-diagnostic coupled with autonomous identification of proper preventive responses on negative trends are critical in order to keep astronauts healthy.