Past neurobiological studies on depression documented various frontal lobe dysfunction and it has been reported that some dysfunction persists even after depressive symptoms disappear.The aim of the present talk is to demonstrate wide range of hypofrontality or frontal lobe-related dysfunction in major depressive disorder (MDD) even in the remitted stage.We used cognitive/neuropsychological approach as well as neuroimaging studies including Single Photon Emission Tomography (SPECT) and Near Infrared Spectroscopy (NIRS).The neuropsychological studies demonstrated that executive dysfunction as indexed by the Wisconsin Card Sorting Test, Stroop task, and verbal fluency task remained even in a remitted state in MDD patients.However, the patterns of residual impairment were different between young and elderly patients.The fnctional neuroimaging studies using SPECT and NIRS both demonstrated significant prefrontal hypoactivities in MDD.Quantitative analyses of SPECT showed decreased regional cerebral blood flow (rCBF) in the regions including anterior ventral and dorsal medial prefrontal cortex.Similar hypofrontality was confirmed by using NIRS during the verbal fluency task.However, even after successful pharmacotherapy with antidepressants, most of such ypofrontality remained unchanged.Neural circuits including bilateral medial and dorsolateral frontal cortices may reflect underlying and continuous pathognomonic brain dysfunction of depression.