Higher education is coming under increasing scrutiny, both publically and within academia, with respect to its ability to appropriately prepare students for the careers that will make them competitive in the 21st-century workplace. At the same time, there is a growing awareness that many global issues will require creative and critical thinking deeply rooted in the technical STEM (science, technology, engineering, and mathematics) disciplines. However, the existing and ingrained structures of higher education, particularly in the STEM fields, are not set up to provide students with extensive skill development in communication, teamwork, and divergent thinking, which is needed for success in the knowledge economy. In 2011 and again in 2014, an international conference was convened to bring together university leaders, educational policymakers and researchers, and funding agency representatives to discuss the issue of institutional transformation in higher education, particularly in the STEM disciplines. Central to the issue of institutional transformation is the ability to provide new forms of instruction so that students can gain the variety of skills and depth of knowledge they will need. However, radically altering approaches to instruction sets in motion a domino effect that touches on learning space design, instructional technology, faculty training and reward structures, course scheduling, and funding models. In order for one piece to move, there must be coordinated movement in the others, all of which are part of an entrenched and interconnected system. Transforming Institutions brings together chapters from the scholars and leaders who were part of the 2011 and 2014 conferences. It provides an overview of the context and challenges in STEM higher education, contributed chapters describing programs and research in this area, and a reflection and summary of the lessons from the many authors’ viewpoints, leading to suggested next steps in the path toward transformation.