Podostemaceae, a family of plants restricted to river rapids and waterfalls, are widely reported to have a high degree of local species endemism. We tested this idea for Neotropical members of the family using historical records, herbarium holdings, personal field collections, and geographic information systems analyses. In contrast to estimates of endemism based on the landmark studies of P. van Royen (66%), we report 15%–37% based on current taxonomy. Examples of regional endemism, based on extent of occurence and longest geographic axis measures, are discussed for a subset of species. Major hydrographic regions (Amazon River System, Paraná River System) and major areas (eastern Brazil) are shown to possess largely unique podostemad floras. We propose rivers and river systems as the most appropriate units to assess endemism for Podostemaceae, and consider one-river and two-river endemics as narrowly distributed. Limitations in the current taxonomy are discussed relative to establishment of meaningful estimates of local species endemism. We provisionally apply IUCN assessment categories to Neotropical Podostemaceae and report that approximately one third of the species fall into one of three categories: Data Deficient (DD), Least Concern (LC), and Vulnerable (VU). Ten species are Critically Endangered (CR). Species of Podostemaceae are restricted to an environment that has experienced major human impacts—tropical rivers. Large dams make long reaches of rivers inhospitable. Expanded use of hydropower in Latin America will exacerbate the problem.