This special issue provides insight into global conservation science by analyzing a 5-year, $12.5 million global marine conservation science and policy program that included over 50 studies in four priority regions involving over 100 scientists and numerous partners. In doing so, it provides reflections on critical challenges for any conservation science program that is intended to inform policymaking, including how to (1) ensure that science process and products influence conservation actions, (2) build global learning from a network of site-based projects, (3) strengthen in-region capacity, and (4) manage relationships across scales among scientists, conservationists, headquarters, and field-based staff. Information is presented on the development and progress of the program as a whole in addition to specific articles covering each of four focal geographic areas: Belize, Brazil, the Eastern Tropical Pacific Seascape, and Fiji.