Alzheimer's disease (AD) is the most common cause of mental impairment in late life and is estimated to afflict nearly half of older adults who live beyond age 85. Although progressive dementia is a cardinal feature of patients with AD, age at symptomatic onset, rate of progression, and specific signs and symptoms vary widely. This clinical heterogeneity appears to arise in part from interindividual differences in the precise molecular events that contribute to the pathophysiology of AD, as well as from nonuniform or multifocal patterns of brain degeneration that occur during the early to middle stages of dementia. The goals of this review are to cover the substantial progress that has been made over the past 5 years in the major thematic areas of research in AD and to assemble these individual findings into a more integrated picture of the pathophysiology of the disorder. The results may have important implications for the treatment or prevention of AD.