This chapter deals with brain imaging techniques. MRI and computer tomography (CT) scans have been used to identify changes in brain morphology in major depressive disorder (MDD). Functional MRI (fMRI), positron emission tomography (PET), and single photon emission computer tomography (SPECT) have all been utilized to identify regions of the brain that are differentially activated in MDD when compared to healthy control subjects. Altered correlation of activity between the frontal lobe and the amygdale has been reported during fMRI studies of patients with MDD. Both bipolar disorder and MDD are likely heterogeneous conditions with different molecular, cellular, genetic, or environmental causes that produce the same clinical phenotype of the disorder. Technical advances in neuroimaging techniques may allow for new questions to be asked into the biological underpinnings of mood disorders and may be used to predict responses to treatments.