Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q₁₀ (CoQ₁₀), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ₁₀ deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ₁₀ in the cell, which is determined by the severity of the mutation. Primary CoQ₁₀ deficiency is unique among mitochondrial disorders because early supplementation with CoQ₁₀ can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ₁₀ deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.