The southeastern U.S. holds a disproportionate fraction of U.S. biodiversity and imperiled species, concentrated in richness and rarity hotspots. Edward O. Wilson’s 2016 book Half Earth: Our Planet’s Fight for Life highlighted the Southeast as a biodiversity hotspot and called for massively increased protected status. The greatest concentration of imperiled species in the conterminous U.S. occurs in SW Virginia. The southern Appalachian Mountains are known for both biodiversity of and threats to fishes, freshwater mussels, plants, salamanders, and cave species, while the coastal plains have a great diversity of reptiles, amphibians, plants and fishes, many of which are imperiled. Many species with narrow geographic ranges are found in the Appalachian and Cumberland Mountains and in the ~375,000 confluence-to-confluence stream reaches in the Southeast, a stream density that is almost twice that of the rest of the U.S. These facts, combined with both regional poverty and types of natural resource use and management (e.g., dams of the Tennessee Valley Authority; coal mining, mountaintop removal and attendant water pollution; agriculture), make conservation measures urgent. Such anthropogenic impacts will impede species’ abilities to respond to the great climate changes that the Southeast is expected to undergo. Downscaled regional projections of temperature and precipitation predict increased frequencies of heat waves and extreme precipitation events, but there is a high degree of uncertainty in climate projections. On average, some parts of the Southeast are projected to experience drier conditions under a changing climate while others become wetter, with magnitudes and patterns of projected changes dependent on which general circulation model is considered. It is therefore timely for ESA members, assembled in the Southeast in 2019, to examine how this great diversity came to exist, where it is located, its status, and how climate change, land use changes, and introduced species will challenge it. Palynological and other paleo data elucidate the biotic history, and combined environmental and niche models give a first cut at predicting the fate of individual species. Examination of species’ ecological and evolutionary responses to environmental change focuses these predictions and suggests the nature and location of effective conservation measures. Their relevance to the Southeast aside, these are current and active research topics, and the symposium assembles speakers working at the forefront of these topics. Their research synthesizes various empirical and observational data with modeling techniques to generate predicted patterns of biodiversity and estimate uncertainty of such predictions.