ABSTRACT: Alzheimer disease (AD) is a significant health problem with increasing costs to patients, families, and society. Historically, AD has been diagnosed clinically in living patients using patient history and cognitive testing, approaches with limited sensitivity and specificity. Definitive diagnosis becomes possible only after the patient’s death, when physical evidence of the disease process is found upon autopsy. By the time signs and symptoms are sufficient for clinical diagnosis, brain pathology is often quite advanced, limiting benefits of treatment. New techniques have been developed in recent years allowing clinicians to see evidence of the AD pathophysiological process in vivo, allowing more definitive diagnosis while the patient is still alive. In vivo methods able to identify AD in its earliest stages, before the development of the cognitive impairment that allows clinical diagnosis, could enable treatment to begin before pathology is advanced. In 2011, the U.S. NIH National Institute on Aging and the Alzheimer’s Association issued new diagnostic guidelines for AD allowing use of biomarker and imaging techniques in addition to clinical criteria. This article describes these new techniques and discusses how they might be used in the diagnosis and management of AD.