Abstract This article presents a 21st Century agenda for Amazonian conservation. The agenda calls for developing a system of refugia and a scientific methodology for predicting impacts of the infrastructure development vision for the region. It also calls for a collaborative approach to conservation planning, in the interest of fruitful engagement with decision‐makers and stakeholders. The ideas explored here emerged from the collaboration of peers over a decade, which culminated in a panel presentation, Scientific Analysis, and Simulation Models to Support Conservation and Development Decision‐Making , at the Tools and Strategies Workshop held at the University of Florida in October, 2017.