A variety of technical assistance organizations have been created in the last 20 years to help public schools implement reforms to improve their perfor- mance. These organizations vary in size, sponsorship, and focus, but their creation rests on the common premise that the reforms needed in the schools to educate all children to high standards require strong external stimuli and resources and knowledge beyond what are ordinarily available in public school systems (McDonald, McLaughlin, & Corcoran, 2000). Accordingly, these technical assistance organizations forge partnerships with school systems under pressure to improve their performance. Working across the boundaries of the educational system, these organizations serve as catalysts for reform, offering schools and districts expertise and other resources needed to make the desired changes. Dedicated to the implementation of reforms, they are presumed to be free of the ordinary interests and ordinary political pressures and, therefore, more likely to be able to overcome the inertia and resistance that often block reform in public bureaucracies like school systems. Researchers have not paid sufficient attention to these organizations, yet they play an increasingly important role in the improvement of public education. To stimulate more interest in these organizations, and in understanding what makes them effective, we report here on the Merck Institute for Science Education (MISE). For nearly 10 years, the Consortium for Policy Research in Education (CPRE) has evaluated MISE’s partnership with four school districts in New Jersey and Pennsylvania, providing MISE staff with feedback on the progress of their work and assessing MISE’s impact on schools, teachers, and students. This long-term relationship has provided an extraordinary opportunity for both CPRE and MISE staff to gain insights into how a technical assistance organization works with school districts to change classroom practice. The story of MISE, and its efforts to bring about instructional reforms in science, is a story of vision, collaboration, learning, and persistence. It is also a success story that offers important lessons for other intermediary organizations working with school districts to improve teaching and learning.