Mitochondrial dysfunctions are associated with the pathogenesis of various brain disorders, including Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, Leigh syndrome and autism spectrum disorder. For the study of mitochondrial dysfunction and the development and testing of new therapeutic strategies, in vivo studies with zebrafish (Danio rerio) are of particular interest, due to their biological characteristics, practicality in laboratory maintenance, and high throughput. Here, we discuss genetic and pharmacological models of common mitochondrial dysfunctions and related neurological disorders in rodents and zebrafish, focusing of the growing utility of these fish in modeling mitochondrial pathogenesis of various CNS diseases.