Correct expression of the mitochondrially-encoded genes is critical for the production of the components of the oxidative phosphorylation machinery. Post-transcriptional modifications of mitochondrial transcripts have been emerging as an important regulatory feature of mitochondrial gene expression. Here we review the current knowledge on how the mammalian mitochondrial epitranscriptome participates in regulating mitochondrial homeostasis. In particular, we focus on the latest breakthroughs made towards understanding the roles of the modified nucleotides in mitochondrially-encoded ribosomal and transfer RNAs, the enzymes responsible for introducing these modifications and on recent transcriptome-wide studies reporting modifications to mitochondrial messenger RNAs. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Matthias Soller and Dr. Rupert Fray.