Phenomenological differences between older patients with late- and early-onset depression may reflect differences in aetiology and neuropathological processes involved in these two types of depression. Early- onset depression has been mainly correlated to a family history of depression while late-onset depression has been principally correlated to vascular dysfunction. The same cortical and sub-cortical areas are involved in both types of depression. However, lesions in these brain areas and cognitive impairment are most pronounced in late-onset depression. Based on these observations we propose a common neuroanatomical substrate but different pathophysiological processes implicated in these two types of depression.