Depression and Alzheimer's disease (AD) are among the most prevalent mental disorders in the elderly. Strong evidence suggests that vascular diseases and vascular risk factors are associated with both depression and AD, and could partially explain the coexistence or the concurrent onset of these two diseases. In particular, endothelial dysfunction appears to play a critical role in the neurobiology of depression and amyloid deposition in the brains of patients with AD. Antidepressants have a significant impact on endothelial function. In addition, several drugs used to treat vascular disease or vascular risk factors, such as calcium-channel blockers, angiotensin-converting enzyme inhibitors and statins, have, to variable extents, significant clinical effects on depressive symptomatology or amyloid deposition in AD. Furthermore, preclinical and clinical data suggest that the nitric oxide and VEGF signaling pathways may be of value for the treatment of depression and AD.