The aa₃-type cytochrome c oxidase (CcO) is a heme–copper terminal oxidase present in many bacteria, particularly the α-proteobacteria, and in all mitochondria, which arose from the α-proteobacteria. CcO is a multimeric enzyme, but all of its redox-active metal centers are located within subunits 1 and 2, termed COX1 and COX2. The structure of the redox-active metal centers is completely conserved from α-proteobacteria to humans. Assembly of the metal centers of CcO requires a group of proteins dedicated to the process, the numbers of which always exceed the number of CcO structural subunits. Five key assembly proteins from the α-proteobacteria are also present in mitochondria, but the assembly machinery in mitochondria is much more elaborate and thus requires many more assembly factors. In addition, copper homeostasis in mitochondria is highly regulated and coupled to metal incorporation into CcO. Although investigations over the last 50 years have disclosed the sophistication of the pathways involved in the assembly of the redox-active metal centers of CcO, numerous questions remain. Here, we review the current state of knowledge of the biogenesis and assembly of the catalytic core of CcO and examine the mechanisms of metal center assembly operating in prokaryotes and eukaryotes.