This study is part of an on-going effort to evaluate and monitor river dolphin populations in South America. It comprises the largest initiative to estimate population size and densities of Inia and Sotalia dolphins using statistically robust and standardized methods. From May 2006 to August 2007, seven visual surveys were conducted in selected large rivers of Bolivia, Colombia, Brazil, Ecuador, Peru, and Venezuela in the Amazon and Orinoco river basins. Population sizes of Inia and Sotalia were estimated for different habitats (main river, tributary, lake, island, confluence, and channel). A total of 291 line and 890 strip transects were conducted, covering a distance of 2,704 linear kilometers. We observed 778 Inia geoffrensis, 1,323 Inia boliviensis, and 764 Sotalia fluviatilis. High-density areas were identified (within 200 m from the river banks, confluences, and lakes) and we propose that these constitute critical habitat for river dolphins. High densities of river dolphins seem to coincide with well-managed freshwater protected areas and should be considered as hot spots for river dolphins in South America.