Respiratory complex II (CII) is one of the four membrane-spanning bioenergetic complexes that participate in oxidative phosphorylation. CII also links two essential energy-producing processes, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Functional CII is a multi-cofactor containing tetrameric complex and is conserved across species from prokaryotes to eukaryotes. Mutations in the genes encoding individual subunits of this complex or dedicated assembly proteins that are referred to as assembly factors, are associated with human pathologies. There is considerable information available on the structure and function of mature CII from a range of organisms. However, the process of maturation of the individual cofactor-containing subunits and their assembly into mature CII is not well understood. Recent functional and structural data from our research document roles of two assembly factors, SDHAF2 and SDHAF4, in guiding the maturation and assembly of the SDHA subunit of CII, which contains the active site for succinate oxidation to fumarate. The data also show how intrinsic disorder of assembly factors plays a significant role in regulating the correct assembly of eukaryotic CII.