Alzheimer’s disease (AD) affects cognition, behavior, and functional activities. Because the disease is most common among the elderly, dissociating pathological changes from those that are the result of normal aging is critical. In the current chapter, we discuss how structural magnetic resonance imaging has been used to characterize morphological changes, including gray and white matter macro- and microstructure, in normal aging and in AD and how these morphological changes are associated with cognitive abilities. AD has well recognized morphological changes, such as whole brain and temporal lobe atrophy, which are particularly striking in patients in more severe stages. Although in earlier stages, there is considerable overlap in morphological findings, normal aging is characterized by relatively greater frontal volume loss, whereas AD shows greater posterior involvement, particularly in the mesial temporal lobe.