© 2015 Elsevier B.V. Epigenetic modifications of the nuclear genome have been well studied and it is established that these modifications play a key role in nuclear gene expression. However, the status of mitochondrial epigenetic modifications has not been delved in detail. The recent technological advancements in the genome analyzing tools and techniques, have helped in investigating mitochondrial epigenetic modifications with greater resolution and studies have indicated a regulatory role of the mitochondrial epigenome. Association of mitochondrial DNA methylation with various disease conditions, drug treatment, aging, exposure to environmental pollutants etc. has lent credence to this belief. Herein, we have reviewed studies on mitochondrial epigenetic modifications with a focus to comprehend its regulatory role in gene expression and disease association.