Reviewed here is the current knowledge of proton transport mechanisms in mammals. The emphasis is on gastric acid secretion and the role of the H+, K+-ATPase, but molecular and cellular information on other P-, V- and F-type H+-ATPases, in bone, kidney, plants and yeast, as well as other cation ATPases, are included for important comparisons. The role of proton/anion antiports, symports and channels in proton transport is discussed. Further attention is given to the regulation of proton transport mechanisms and cellular mechanisms to resist damage from highly acidic environments.