Mitochondrial genetics has become an emerging area of research in the field of modern therapeutics. Mitochondrial genome is the source of 13 polypeptides which are components of subunits of complexes of electron transport chain and are used in the generation of ATP by oxidative phosphorylation. Any mutation and/or defects in these mitochondrial genes may cause diseases ranging from neurodegenerative diseases, diabetes mellitus to cancer. In an ideal condition mtDNA should be mutation free. There are various mechanisms for the repair of diseased cell or mitochondrial DNA. Nowadays, nucleic acid based therapeutics has become of interest and represent a new area of research. However, problem consistently encountered is safe and effective delivery of DNA to the mitochondria for therapeutic benefits. There are numerous barriers which are to be surpassed for successful delivery of nucleic acid to the cell interior and ultimately to the mitochondria. For efficient and effective DNA delivery to the mitochondrial matrix, a suitable carrier system is required to be designed and developed. In the present review we have discussed briefly about mitochondrial DNA and related diseases, various barriers encountered in the delivery of DNA, internalization processes, delivery strategies and methods for targeted delivery of DNA to the mitochondria.