We illustrate 2 patients with depression who attained dramatic improvement of energy loss and fatigue when treated with cabergoline, a dopamine agonist, and milnacipran, a serotonin-noradrenalin reuptake inhibitor. Although the biologic basis of energy, motivation, and fatigue in association with depression remains unknown, some reports suggest that the decrease of noradrenalin and dopamine in the brain are particularly related to these symptoms. Therefore, treatment strategy that enhances these two monoamine neurotransmissions may be appropriate for getting a boost in energy and eliminating fatigue in patients with depression. These cases suggest that further studies are warranted to confirm the potential benefit of this strategy in the treatment of patients with depression who failed to attain complete remission due to residual symptoms including energy loss and fatigue refractory to previous treatments.