AbstractCoenzyme Q10 (CoQ10) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ10 is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ10 supplementation. CoQ10 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 CoQ10 (primary CoQ10 deficiencies) or in genes not directly related to CoQ10 biosynthesis (secondary CoQ10 deficiencies). Respiratory chain defects, ROS production, and apoptosis contribute to the pathogenesis of primary CoQ10 deficiencies. In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:183–188.