Family Percichthyidae, Subfamily Percichthyinae and its genera Percichthys and SANTOSIUS gen. nov. are diagnosed. P. trucha, P. hondoensis, P. lonquimayiensis, P. sandovali sp. nov. and P. melanops are included in the genus Percichthys; all of these species are described. Guayquichthys ferugloi Dolgopol is considered a synonym of P. hondoensis. The Family Perciliidae is diagnosed, and Percilia gillissi and P. irwini are redescribed. The Family Percichthyidae is represented in the fossil record by Percichthys P. hondoensis in the Eocene of Argentina, by P. lonquimayiensis and P. sandovali in the Upper Paleocene of Chile; and by Santosius antiquus comb. nov. (P. antiquus) in the Upper Tertiary of Brazil. Even in the Tertiary, the freshwater percichthyids were distributed in Brazil and southern South America; now they are restricted to southern Chile and Argentina. A comparison between South American members of Percichthyidae, Perciliidae and some serranids is made, and some diagnostic characters are discussed.