Alzheimer's disease (AD) starts at a molecular level possibly decades earlier than could be detected by neuropsychological tests (NPTs). Neuropathological and neuroimaging data suggest that amyloid accumulation precedes the clinical onset of AD. Disease-modifying agents would have to be used early to alter the course of AD. Therefore, preclinical diagnosis is necessary. Structural and functional neuroimaging are superior for detection of the earliest stages of AD. Magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques, including amyloid visualization, will have therapeutic importance for prevention as well as intervention as further refinements of current imaging techniques and biochemical markers occur. Neuropsychological tests measure the effect of pathology for an individual based upon norms obtained from an artificial population-often white and relatively highly educated. Unless serial NPTs are performed, the individual is compared to a population to which they may not conform. Neuroimaging can provide objective measures of preclinical disease state and, when measured serially, rate of change. Such information can be used in prevention trials.