The urea cycle occurs widely in vertebrates, serving different functions in different lineages. In elasmobranchs, where it contributes to osmolar balance, the product urea itself is functionally useful. In other vertebrates the synthesis of urea serves functions other than provision of urea. In air-breathing fish, amphibians, and mammals ureagenesis generates protons that contribute to pH homeostasis by titration of metabolically produced bicarbonate, and in ruminants this function is supplemented by large-scale transport of bicarbonate in the form of urea from tissues to the rumen. Disposal of ammonium in ureotelic species generally and delivery of ammonium to the rumen in ruminants appear to be consequences of pH-modulated ureagenesis rather than primary functions. Because only regulatory changes are required for its development from the arginine synthetic pathway and because it consumes no metabolites and relatively little ATP, the urea cycle is a uniquely suitable source of the protons that are needed for maintenance of pH homeostasis.