Updated publication reference for PubMed record(s): 31614365. Proteins in saliva are needed for preprocessing food in the mouth, maintenance of tooth mineralization, and protection from microbial pathogens. Novel insights into human lineage-specific functions of salivary proteins and clues to their involvement in human disease can be gained through evolutionary studies, as recently shown for salivary amylase AMY1 and salivary agglutinin deleted in malignant brain tumors 1/gp340. However, the entirety of proteins in saliva, the 20 salivary proteome, has not yet been investigated from an evolutionary perspective. Here, we compared the proteomes of human saliva and the saliva of our closest extant evolutionary relatives, chimpanzees and gorillas, using macaques as an outgroup, with the aim to uncover features in saliva protein composition that are unique to each species.We found that humans produce a waterier saliva, containing less than half total protein than great apes and OldWorldmonkeys. For all major salivary proteins in humans, we could identify counterparts in chimpanzee and gorilla saliva. However, we 25 discovered unique protein profiles in saliva of humans that were distinct from those of nonhuman primates. These findings open up the possibility that dietary differences and pathogenic pressures may have shaped a distinct salivary proteome in the human lineage.