The increasing prevalence of Alzheimer's disease and the devastating consequences of late-life dementia motivates the drive to develop diagnostic biomarkers to reliably identify the pathology associated with this disorder. Strategies to accomplish this include the detection of altered levels of tau and amyloid in cerebrospinal fluid, the use of structural MRI to identify disease-specific patterns of regional atrophy and MRI T(1)rho to detect disease-related macromolecular protein aggregation, and the direct imaging of amyloid deposits using positron emission tomography and single photon emission computerized tomography. Success will facilitate the ability to reliably diagnose Alzheimer's disease while the symptoms of brain failure are mild and may provide objective measures of disease-modifying treatment efficacy.