The total South Florida ecosystem encompasses all natural areas that were once interconnected and embedded within the vast Everglades basin that originally extended from coast to coast and from the upper Kissimmee basin headwaters to Florida Bay, Biscayne Bay, the Gulf of Mexico, and Caloosahatchee and Indian River Lagoon estuaries. Restoration of this system will be successful once defining characteristics of the pre-altered system are recovered. Defining characteristics of the ecosystem are 1) abundant large vertebrates and aquatic prey bases, 2) animals with large spatial requirements, 3) healthy, dynamically sustainable estuaries, 4) oligotrophic freshwater wetlands, and 5) complex landscape mosaics and interactions. These defining characteristics have been altered by three external drivers that create stressors on the system: water management, land-use management and development, and climate change and sea-level rise. Stressors on the South Florida ecosystem include loss of spatial extent; loss of connectivity; altered geomorphology and topography; altered volume, timing, and distribution of regional hydropatterns; input of nutrients; altered fire patterns; and introduction and spread of exotic plants and animals. The Total System Conceptual Ecological Model links stressors to changes in the defining characteristics through major working hypotheses of cause-and-effect relationships. The linkages (ecological effects) relate to hydroperiod and depth patterns, sheet flow, salinity gradients, nutrient status and dynamics, fire patterns, habitat availability, and marsh aquatic fauna prey bases. For each defining characteristic, key ecological indicators are identified to collectively track the decline and restoration of the ecosystem.