For decades, the mitochondria have been primarily viewed as biosynthetic and bioenergetic organelles generating metabolites for the production of macromolecules and ATP, respectively. We have elucidated mitochondria have a third distinct role whereby they participate in cellular signaling processes through the release of reactive oxygen species (ROS) and the metabolite L-2hydroxyglutrate (L-2HG). Our work has implicated the necessity of mitochondrial ROS as second messengers for multiple biological processes including hypoxic activation of HIF dependent gene transcription, cellular differentiation, and immune cell activation. We have also identified that mitochondria release the metabolite L-2HG, which increases histone and DNA methylation to control hematopoietic stem cell (HSC) differentiation and regulatory T cell (Treg) function, respectively. Thus, mitochondria serve as signaling organelles. It is important to note that there are other mitochondrial signals such as mtDNA for inflammation and cytochrome c for apoptosis that are also active areas of research into the role of mitochondria as signaling organelles.