Bipolar disorder (BPD) is characterized by pathophysiological changes to the visceromotor network, disrupting the regulation of endocrine and autonomic responses to stress, and hence emotion and behavior. Specifically, reductions in gray matter volume and a concomitant increase in glutamatergic neurotransmission, is observed in the pregenual (pgACC) and subgenual anterior cingulate cortex (sgACC), the orbitofrontal, frontal polar and ventrolateral prefrontal cortex (PFC), the posterior cingulate, ventral striatum, and hippocampus. While increased glutamatergic signaling is equally salient in the amygdala, the data are conflicting on the nature of volumetric changes in this region. Neuroreceptor imaging data provide preliminary evidence for serotonin, serotonin transporter (5-HTT), dopamine receptor, and cholinergic system dysfunction in BPD. Oft-reported abnormalities of the deep frontal and basal ganglia white matter, and enlargement of the third and lateral ventricles are likely associated with cerebrovascular disease. Mood stabilizers and antidepressant drugs may attenuate pathological limbic activity, and increase neurotrophic processes, restoring balance to the system.