The pathogenesis of major depression (MD) remains unclear despite intensive research in the last decades which brought up a multitude of findings illustrating the complexity of this disorder. In this paper we will summarize the evidence pointing towards a structural alteration of the basal limbic system in MD and depression in Parkinson's disease (PD). Transcranial ultrasound and MRI studies in both depressive syndromes revealed altered signal intensity of the brainstem midline comprising fibre tracts of the basal limbic system. The hypothesis of a structural disruption of the basal limbic system is supported by biochemical and histopathological findings. The similarity of findings in MD and depression in PD might reflect a relationship between MD and neurodegenerative disorders.