Cytochrome c oxidase (CcO) is an oligomeric complex localized within the mitochondrial inner membrane. Assembly of the active oxidase complex requires the coordinate assembly of subunits synthesized in both the cytoplasm and the mitochondrion. In addition, assembly is dependent on the insertion of five types of cofactors, including two hemes, three copper ions, and one Zn, Mg, and Na ion. A series of accessory proteins are critical for synthesis of the heme A cofactor and insertion of the copper ions. This Account will focus on the steps in the coordinate assembly of CcO subunits, the formation of heme A, and the delivery and insertion of copper ions.