There is an urgent need to develop the underlying theory and principles of ‘‘sustainability science,’’ based on an understanding of the fundamental interactions between nature and humans. This requires a new research and education paradigm that embraces biocomplexity, integrates the physical, biological, and social sciences, and uses a coupled, human–natural systems approach. An initiative aligned with this paradigm and approach, and centered on the Hawaiian Island’s unique mountain-to-sea ecosystems, is developing at the University of Hawai‘i. These ecosystems, extending from upland tropical forests to the fringing coral reefs, correspond to the roughly wedge-shaped catchments, traditionally called ahupua‘a in the Hawaiian language. Despite the collapse of the ahupua‘a system and, tragically, the Native Hawaiian population, its legacy of ecological and cultural stewardship remains. This legacy, and the potential of these ecosystems as microcosms for addressing the core questions of sustainability science, has provided the impetus for a growing number of projects employing a social– ecological systems perspective. An overview of three projects that employ a ‘‘learning community’’ approach and cultural stewardship perspective inspired by the ahupua‘a system is provided. These include the Ecosystems Thrust Area of Hawai‘i EPSCoR, a U.S. National Science Foundation research infrastructure program, focused on ecosystem research and monitoring activities; a sustainability curriculum program, Malama I Ka ‘Aina, of the College of Education; and a project that builds on programs of the Division of Ecology and Health and its affiliated AsiaPacific Center for Infectious Disease Ecology, linking ecosystem resilience and infectious diseases.