The Caribbean Sea and its watersheds show signs of environmental degradation. These fragile coastal ecosystems are susceptible to environmental impacts, in part because of their oligotrophic conditions and their critical support of economic development. Tourism is one of the major sources of income in the Caribbean, making the region one of the most ecotourism dependent in the world. Yet there are few explicit, long-term, comprehensive studies describing the structure and function of Caribbean ecosystems. We propose a conceptual framework using the environmental signature hypothesis of tropical coastal settings to develop a series of research questions for the reef–sea-grass–wetland seascape. We applied this approach across 13 sites throughout the region, including ecosystems in a variety of coastal settings with different vulnerabilities to environmental impacts. This approach follows the strategy developed by the Long Term Ecological Research program of the National Science Foundation to establish ecological research questions best studied over decades and large spatial areas.