Evidence from diverse areas of research including chronobiology, metabolomics and magnetic resonance spectroscopy indicate that energy dysregulation is a central feature of bipolar disorder pathophysiology. In this paper, we propose that mania represents a condition of heightened cerebral energy metabolism facilitated by hyperglycolysis and glutaminolysis. This unique metabolic state may be initiated in an attempt to restore energy to neurons under conditions of impaired oxidative glucose metabolism occurring in the depressed state.When brain glucose metabolism becomes impaired, neurons can utilize glutamate as an alternative substrate to generate energy through oxidative phosphorylation. Glycolysis in astrocytes fuels the formation of denovo glutamate, which is used as a mitochondrial fuel source in neurons via transamination to alpha-ketoglutarate and subsequent reductive carboxylation to replenish tricarboxylic acid cycle intermediates. Upregulation of glycolysis and glutamate metabolism in this manner causes the brain to enter a state of heightened metabolism and excitatory activity which we propose to underlie the subjective experience of mania.Under normal conditions, this mechanism serves an adaptive function to transiently upregulate brain metabolism in response to demanding mental tasks, a perceived danger or challenge in the environment, or injury. However, when recruited in the long term to counteract impaired oxidative metabolism it may become a pathological process leading to excitotoxicity. In this article, we develop these ideas in detail, present supporting evidence and propose this as a novel avenue of investigation to understand the biological basis for mania.