There are a number of potential neurochemical alterations in the dorsolateral prefrontal circuit that are related to the clinical expression of bipolar disorder. This chapter focuses on translational studies that integrate neurochemical and neuroanatomical information to better understand the pathophysiology of bipolar disorders. There are three major frontal-subcortical circuits that constitute the corticolimbic network: dorsolateral prefrontal, lateral orbitofrontal, and anterior cingulate. Several techniques have been developed that allow for non-invasive assessment of neurochemistry. Ligand-specific positron emission tomography (PET) and single photon emission computed tomography (SPECT) permit regional measurement of monoamines and other neurochemicals, which are thought to be crucial to affective processes. There have been numerous findings of peripheral serotonergic dysfunction in bipolar disorder, including decreased serotonergic reuptake in platelets. The neurochemistry of corticolimbic circuits presents additional challenges for clarifying the neurochemical basis of dysregulation that has been observed in functional neuroimaging studies.