Mitochondrial succinate dehydrogenase (SDH) whose regulation and assembly requires additional factors that are beginning to be discovered. SDH that has been subject to a focused but significant renaissance consists of four unclearly encoded subunits. Mutations in the structural gene subunits (SDHA, B, C and D) of the complex itself cause a variety of human diseases. SDH-A pathogenic mutations have been reported to cause an encephalomyopathy in childhood, while mutations in the genes encoding the other three subunits have been associated only with tumour formation. It participates in the electron transport in the respiratory chain, and in succinate catabolism in the Krebs cycle. SDH is also called the electron transport chain complex II and it has been the least studied of the mitochondrial respiratory five complexes. It has seen renewed interest, because of its role in human disease. Following a brief description of SDH genes and subunits, we examine the properties and roles of SDH in the mitochondria. The mechanisms underlying the pathogenesis of SDH mutations are beginning to be understood. We stress the importance of SDH in a number of diseases and the need to better delineate the consequences of SDH deficiency in human.