The Everglades and South Florida ecosystems are the focus of national and international attention because of their current degraded and threatened state. Ecological risk assessment, sustainability, and ecosystem and adaptive management principles and processes are being used nationally as a decision and policy framework for a variety of types of ecological assessments. The intent of this study is to demonstrate the application of these paradigms and principles at a regional scale. The effects-directed assessment approach used in this study consists of a retrospective, eco-epidemiological phase to determine the causes for the current conditions and a prospective predictive risk-based assessment using scenario analysis to evaluate future options. Embedded in these assessment phases is a process that begins with the identification of goals and societal preferences which are used to develop an integrated suite of risk-based and policy relevant conceptual models. Conceptual models are used to illustrate the linkages among management (societal) actions, environmental stressors, and societal/ecological effects, and provide the basis for developing and testing causal hypotheses. These models, developed for a variety of landscape units and their drivers, stressors, and endpoints, are used to formulate hypotheses to explain the current conditions. They are also used as the basis for structuring management scenarios and analyses to project the temporal and spatial magnitude of risk reduction and system recovery. Within the context of recovery, the conceptual models are used in the initial development of performance criteria for those stressors that are determined to be most important in shaping the landscape, and to guide the use of numerical models used to develop quantitative performance criteria in the scenario analysis. The results will be discussed within an ecosystem and adaptive management framework that provides the foundation for decision making.