Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness compared to control subjects. There are many different determinants of plasma tHcy concentration, including the presence of vascular disease. The presence of vascular disease may contribute to cognitive impairment. Clarification of the role of vascular risk factors in mental illness is important because most are modifiable, in contrast to other risk factors, such as age and genetics. In this review, we summarize the findings of our investigations of vascular disease and plasma tHcy level in elderly patients with mental illness. Elevated plasma tHcy concentration in elderly patients with mental illness was mainly associated with the presence of vascular disease and was not related to the specific psychogeriatric diagnosis. Furthermore, it seems possible that the control of conventional vascular risk factors could be guided by the level of plasma tHcy, serum cystatin C, serum N-terminal pro-brain natriuretic peptide, and serum C-reactive protein.