Recent findings suggest that damaged mitochondrial DNA (mtDNA) may play a role in the development of Leber's hereditary optic neuropathy, Huntington's, Parkinson's and Alzheimer's disorders, as well as in that of encephalomyopathies. The mtDNA consist of 16,569 base pair and encodes 13 polypeptides, 2 ribosomal RNAs and 22 transfer RNAs. It is much more injurable than the nuclear DNA (nDNA) and since mtDNA participates in the synthesis of respiratory chain enzymes, therefore, its damage may result in neuronal cell death. The present paper summarizes these novel mechanisms and potential therapeutic strategies with regard to neurological disorders.