Neuronal degeneration is a key feature of both Alzheimer disease (AD) and vascular dementia (VaD). Although the exact cause(s) of neurodegeneration in AD is uncertain, strong candidates are beta-amyloid and neurofibrillary tangles (NFT) within neurons. VaD arises as a consequence of ischemic insults such as hemorrhage and hypoperfusion that trigger neurodegeneration by depriving the cells of oxygen and glucose. The initial insults in AD and VaD result in regional differences in the pattern of neurodegeneration, with cholinergic and glutamatergic neurons being particularly vulnerable in AD, and neurons of whatever neurochemical phenotype close to the vascular insult being more at risk of death in VaD. Although the initial trigger of neurodegeneration and the population of neurons affected differ in AD and VaD, there is considerable overlap in the downstream pathways that mediate cell death. As a consequence there are, therefore, a number of levels in the cytotoxic pathway common to AD and VaD at which a neuroprotective agent might be targeted.