Cytochrome c oxidase (COX), the terminal enzyme of electron transport chains in some prokaryotes and in mitochondria, has been characterized in detail over many years. Recently, a number of new data on structural and functional aspects as well as on COX biogenesis emerged. COX biogenesis includes a variety of steps starting from translation to the formation of the mature complex. Each step involves a set of specific factors that assist translation of subunits, their translocation across membranes, insertion of essential cofactors, assembly and final maturation of the enzyme. In this review, we focus on the organization and biogenesis of COX.