Cytochrome c oxidase (CcO) is a terminal protein of the respiratory chain in eukaryotes and some bacteria. It catalyzes most of the biologic oxygen consumption on earth done by aerobic organisms. During the catalytic reaction, CcO reduces dioxygen to water and uses the energy released in this process to maintain the electrochemical proton gradient by functioning as a redox-linked proton pump. Even though the structures of several terminal oxidases are known, they are not sufficient in themselves to explain the molecular mechanism of proton pumping. Thus, additional extensive studies of CcO by varieties of biophysical and biochemical approaches are involved to shed light on the mechanism of proton translocation. In this review, we summarize the current level of knowledge about CcO, including the latest model developed to explain the CcO proton-pumping mechanism.