Over the last decade, scientists and science policy-makers have argued that the current science and technology research portfolio has become too conservative and encourages only incremental advances. In consequence, a number of government and privately funded programs, especially in the United States and Europe, have begun to support pioneering or “transformative” research -- research that has the potential to radically change our understanding of science, shifting paradigms and opening avenues of innovation. While the goal of promoting potentially transformative research is widely shared, the means to do so range from supporting exceptional individuals (e.g., the U.S. National Institutes of Health’s Pioneer program) or small groups (e.g., the European Research Council’s Synergy Program or the U.S. National Science Foundation’s CREATIV program) through building transformative centers or instruments, such as the synthesis centers that catalyze distinctive forms of research collaboration, or instruments such as the Large Hadron Collider. This symposium will explore the promise and challenge of transformative research, specifically addressing policy and program design, peer review and selection, research collaboration, and assessment. Doing so will initiate a “science of transformative research” that will improve understanding of scientific change, inform policy, and guide practice from the level of program design and management to collaborative organization and process.