Most of the world’s liquid freshwater is contained in a small number of very large lakes. The narrow littoral zones of these lakes comprise a small fraction of total lake area, but are nevertheless vast, extensive habitats that have been the sites of numerous species radiations in freshwater. We used literature data to examine the spatial distribution of fish, mollusk, crustacean and insect species in ~15 of the world’s largest freshwater lakes.  Most fish species were associated with littoral or benthic habitats for part of their life history. In lakes with the highest fish diversity, most species were littoral. Both littoral and pelagic invertebrate species richness increased with lake volume. However, littoral invertebrate species richness was generally 3x higher than pelagic zooplankton richness. This estimate is conservative because sampling effort and taxonomic resolution of zoobenthos were consistently lower than for zooplankton, especially in North American lakes. The littoral zone was also the site of high endemism of taxonomic groups with limited dispersal potential (e.g., cichlid fishes, gastropods, amphipods). Despite the small fraction of total lake habitat available to littoral species, littoral zones support the majority of fish and invertebrate diversity in world’s great lakes.  Near shore habitats are also a nexus of human-lake interactions, and thus are particularly vulnerable to habitat modification, pollution, and species introductions.  A more consistent inclusion of littoral zones in the analysis of lake ecosystem function is essential to the conservation of aquatic biodiversity even, and perhaps especially, in very large lakes.