Objective. This article explores the many factors that have been involved in International Space Station (ISS) on-orbit utilization activities, and the approaches that the National Aeronautics and Space Administration is taking to evaluate, communicate, and maximize the value of these activities. Methods. A review of the initiatives, stakeholders, vehicle assembly, science and technology outcomes, and benefits to Earth and space exploration illustrates the evolving nature of this unique microgravity research platform. Results. The ISS partnership works together to implement many strategic approaches to maximizing the ISS platform so that the full potential of this laboratory is realized.