A retrospective view of the critical events and advances in the development of criteria, instruments and algorithms in the diagnosis of Alzheimer's disease. The review is from the vantage point of the National Institute on Aging and its role in the development of the national infrastructure, in the US, for clinical research on dementia. The paper discusses future research needs and challenges for developing new diagnostic armamentarium for early and accurate detection of neurodegenerative processes of dementia in the early prodromal stages or during early mild cognitive impairments.