The data suggest an intriguing link between mitochondrial function and depression that warrants further investigation. First, mitochondria could be considered an important aid in the early diagnosis of MD and contribute to the differentiation of disorders with overlapping symptoms. Similarly, specific forms of mitochondrial dysfunction could be used as biomarkers in the evaluation of the underlying causes of the disease. Lastly, mitochondrial function may represent a promising new target for new antidepressant drugs and the development of customized therapy. Energy, behavior, and therapy constitute a triad of great scientific and health-related interest. To obtain more accurate diagnoses and more effective targeted therapies, it is necessary to invest our energy and resources to better comprehend the role of the what, why, where, and who of energy production, and therefore of mitochondria, and the mechanisms that control normal and pathological human behavior.