Mitochondria are pivotal organelles involved in the regulation of a myriad of crucial biological processes, including cell survival and cell death, rendering mitochondrial dysfunction a relevant step in numerous pathophysiological processes. MicroRNAs (miRNAs) are endogenous small noncoding RNAs that add a new layer of complexity to the control of gene expression. miRNAs function as master regulators and fine-tuners of gene expression, primarily via posttranscriptional mechanisms, and are increasingly demonstrated as a paramount class of endogenous molecules with relevant diagnostic, prognostic, and therapeutic applications. miRNAs and other RNA interference have recently been reported to be present in mitochondria from several species, and we are now beginning to unveil mitochondrial miRNA transport mechanisms, biological function and targets to ascertain their role in this unexplored niche. Here, we describe miRNA biogenesis and present key findings regarding miRNA localization to mitochondria, origin, putative biological function, and implications for human disease.