The mitochondrion, powerhouse of the eukaryotic cell, sits at the center of converging lines of brain-disorder research. Researchers have implicated the organelle in the pathophysiology of distinct conditions such as schizophrenia and bipolar disorder. The motif of convergence extends to results obtained by disparate approaches ranging from molecular and biochemical to clinical, and from empirical to hypothetical. In the brain, energy produced through oxidative phosphorylation in the mitochondrion not only sustains the excitability of the neurons, but also controls intracellular calcium concentration that in turn regulates synaptic transmission, signal transduction, and cellular resilience.