Mitochondria play an important role as an intracellular energy plant and signaling organelle. However, mitochondria also exist outside cells where they could mediate cell-to-cell communication, repair and serve as an activator of the immune response. Their effects depend on the mitochondrial state or the form in which it is present, either as a whole functional structure as fragments or only as mitochondrial DNA. Herein, we provide evidence of why extracellular mitochondria and their varying forms are considered regenerative factors or pro-inflammatory activators. Understanding these aspects will provide the base of their use in therapy or as a biomarker of disease severity and prognosis.