The definitive diagnosis of Alzheimer's disease (AD) is made at autopsy by the presence of abundant neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex, entorhinal cortex, and hippocampus. The two criteria most frequently used by neuropathologists for the diagnosis of AD over the past 12 years are those described by Khachaturian and the Consortium to Establish a Registry for Alzheimer's Disease. Though both have been useful, they have weaknesses and lack validation. The majority of recent studies has shown that NFT in the entorhinal cortex, hippocampus, and neocortex and NP in the neocortex correlate best with severity of dementia in AD. The criteria recommended by the Workshop on Diagnostic Criteria for the Neuropathological Assessment of AD uses semiquantitation of NFT and NP in the neocortex, adds evaluation of the hippocampus and entorhinal cortex, places emphasis on coexisting lesions such as vascular lesions and Lewy bodies, and establishes criteria for general pathologists and more rigorous criteria for the AD research setting. These criteria will require further refinement and validation.