At 1997, Alexopoulos and Krishnan coined the term "vascular depression" to describe depression associated with cerebrovascular disease. Vascular depression included both post-stroke depression, depression occurring after a stroke, and MRI-defined vascular depression in which cerebral infarction is detected by magnetic resonance imaging findings. Post-stroke depression is well known as showing cerebral infarction on imaging modalities as well as clinical symptoms such as localized neurological symptoms related to infarcts. MRI-defined vascular depression demonstrates cerebral infarction on imaging modalities, but there are no clinical symptoms such as localized neurological symptoms or stroke. MRI-defined vascular depression is equivalent to the term "depression with silent cerebral infarction", a condition we studied in the past decade. When the accumulation of infarct lesions induces obstruction in the neuron network related to mood and will exceeds a certain threshold, the patient becomes predisposed to vascular depression. Neurological factors are more prominent than genetic factors or psychosocial stressors in patients with vascular depression due to an accumulation of infarct lesions. Anti-cholinergic drugs and anti-dopaminergic drugs easily induce adverse central nervous system reactions in patients with vascular depression demonstrating prominent neurological factors. Research on vascular depression has contributed to clarifying the onset mechanism of endogenous depression.