The intracellular non-bicarbonate buffering capacity of vertebrate muscle is mainly supported by the imidazole groups of histidine residues in proteins, free L-histidine in some fish species, and histidine-containing dipeptides such as carnosine, anserine, and balenine (ophidine). The proton buffering capacity markedly differs between muscle types and animal species depending on the ability for anaerobic exercise. The capacity is typically high in fast-twitch glycolytic muscles of vertebrates adapted for anaerobic performance such as burst swimming in fishes, prolonged anoxic diving in marine mammals, flight in birds, sprint running in mammalian sprinters, and hopping locomotion in some terrestrial mammals. A high correlation between buffering capacity, concentration of histidine-related compounds in muscle, and percentage of fast-twitch fibers in all vertebrates adapted for intense anaerobic performance clearly supports the idea that proton buffering is the main physiological function of histidine-related compounds.