Mitochondrial function has long been recognized as central to normal physiology and a contributor to a broad range of pathologies. Much of the early research in mitochondrial biology focused on the mechanisms to generate ATP and characterization of mitochondria from highly energetic tissues such as the heart or liver. More recent studies emphasize the role of mitochondria in redox signaling and in less energetic cells such as those in the innate immune system and the vasculature. In this short overview, we discuss some of these recent developments in translational and basic research in mitochondrial pathophysiology. Advanced high throughput analytical techniques are now allowing the assessment of bioenergetic health in human populations and the emergence of the exciting new field of metabolotherapeutics. These have led to the emergence of the new field of redox bioenergetics which encompasses both the canonical aspects of mitochondrial energy production and the organelles' role in cell signaling and disease.