Human spaceflight is entering a new era. The assembly of the International Space Station (ISS) will be completed in 2010.2 Supported by a full six-person crew for the first time, it is ready to put its full capabilities to work. While the ISS partners can be proud of having completed one of the most ambitious engineering projects ever conceived, the world at large also will judge the ISS by what is achieved in the utilization phase. In short, the full success of the ISS Program depends on the utilization achievements in the coming years. The people of countries participating in the ISS will expect no less. For more than 15 years, the ISS partnership mastered financial and technical challenges, and weathered changes in national policies and governments. This mastery proves that nations can persist and achieve ambitious long-term goals that are very difficult. The ISS partnership is a model of what will be needed if an ambitious program of exploration beyond low-Earth orbit (LEO) is to move forward. The present partnership can be enriched by collaboration as we prepare for human exploration beyond Earth's neighborhood, to develop supporting technology, and to explore possible relationships with emerging space agencies. Aside from the ISS itself, the international partnership represents an invaluable achievement. Extension of ISS operations to 2020 and beyond is crucial to maximize use of the ISS facilities. A longer operational phase provides opportunities for new participants who may never have thought of using the ISS. A commitment to extended operations enables programs with long-term objectives, and encourages institutions on Earth to support projects in space. Perhaps most importantly, extended utilization allows opportunities to explore the ISS as a research platform and to realize its full potential. Unique attributes of the ISS that enable research and development (R&D) never before achieved include: (1) continuous access to microgravitya and defined partial gravity, enabling experiments with gravity as a controlled experimental variable; (2) high vacuum and the conditions to create ultra-high vacuum, enabling experiments that would be otherwise compromised by trace molecular species; (3) continuous presence in the space environment, enabling long experiment runs and cumulative sets of experiments; (4) significant power and instrument support services at a low-altitude (310-410 km) vantage point over 90% of the populated surface of the Earth, enabling use of the ISS as a platform for observations of Earth, Earth's atmosphere, and space processes; (5) daily human support and transportation resources enabling testing, modification, and incremental development of R&D test beds, instruments, and research programs. The benefits of ISS can be viewed from many different perspectives. As for other unique laboratories, long lead times to discovery can be associated with the many different disciplines that use the ISS. As scientists representing this broad array of disciplines, the ISS partner nations, and future utilization by all scientists worldwide, we met to discuss R&D on the ISS as the utilization era begins. We have captured the major disciplines, key questions, advantages of the ISS platform, and implications of ISS utilization for advancement of knowledge. The products of the discussion are a vision for the “Era of International Space Station Utilization,” with supporting descriptions of the importance of the ISS to key R&D goals. We are certain that in the century to come, the full utilization of the ISS will be seen as having made transformative contributions to a number of scientific disciplines.