One of Dr Leon Thal's major contributions to Alzheimer's disease (AD) research was the network of clinical trials and his strong commitment to finding effective therapies for both the prevention and treatment of AD in the population. AD and dementia research has matured since the inception of the Alzheimer's Disease Center program from a primary social service problem to clinical-pathologic correlates and better definition of disease to evaluation of measures of cognition, in vivo images of the brain, and then to measures of beta amyloid and tau in vivo and relationship to clinical dementia. Unfortunately, we still do not know the etiology of AD or the relationship to other brain abnormalities such as vascular disease and Lewy bodies. We also do not have good preventive or treatment strategies. Both are badly needed. The critical question is whether this field is ready for a major change in focus from primarily a descriptive science to analytical, longitudinal studies testing new research hypotheses that will lead to better preventive and treatment approaches.