Positron emission tomography (PET) imaging of the protein aggregates amyloid-β (Aβ) and tau has transformed Alzheimer disease (AD) research. Validating PET radiopharmaceuticals for this purpose is a complicated undertaking, requiring initial in vitro and animal studies that define binding affinity, selectivity, and pharmacokinetics. The most convincing and final stage of validation is the comparison between ligand behavior in a PET scan taken during life and the postmortem neuropathological examination. Such projects, entailing the recruitment of terminally ill individuals with a spectrum of dementing disorders and normal cognition, have successfully demonstrated that currently available amyloid PET imaging radiopharmaceuticals are sensitive and specific for the detection of Aβ and have led to their approval by US and international regulatory agencies.