Coenzyme Q[subscript 10] (CoQ[subscript 10]) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ[subscript 10] is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ[subscript 10] supplementation. CoQ[subscript 10] deficiency has been associated with five major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) nephrotic syndrome. In a few patients, pathogenic mutations have been identified in genes involved in the biosynthesis of CoQ[subscript 10] (primary CoQ[subscript 10] deficiencies) or in genes not directly related to CoQ[subscript 10] biosynthesis (secondary CoQ[subscript 10] deficiencies). Respiratory chain defects, ROS production, and apoptosis contribute to the pathogenesis of primary CoQ[subscript 10] deficiencies. In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies. (Contains 1 figure.)