Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions, and ecosystem services. We review the characterization, identification, and meaning of CoEs. Endemics play an increasing and prominent role in nature conservation monitoring and management and in the organization of zoos, aquaria, and botanical gardens. We examine the importance of different groups of organisms and indicators for the characterization of endemic-rich regions, e.g., with regard to the richness of endemics per region and degree of endemism, the importance of heterogeneity in space, continuity in time, isolation, and ex situ management for the survival of endemic species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides, or tsunamis. For conservation purposes, the management of regional land use, zoos, aquaria, botanical gardens, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We find that the ex situ representation of endemics in general is limited, and conservation networks in this regard can be improved. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of endemism, which is linked with human culture including aesthetics, well-being, health, and trade.