OBJECTIVES: Abnormalities in the frontal lobe have been consistently suggested in the pathophysiology of depression. The purpose of this review is to discuss the relationship between the frontal lobe and depression. METHODS: Recent researches on the frontal lobe in depression were reviewed and abnormalities in this region were considered within the context of modern functional neuroanatomy. RESULTS: This paper reviewed evidence strongly implicating the frontal lobe as a key brain structure in depression. CONCLUSION: Taken together, these abnormalities in the function of the frontal lobe implicate interconnected neural circuits in depression and offer suggestions for the themes of future research and treatment. Further research is needed to investigate the association between emotion and the brain in the paradigm of "affective neuroscience".