The occurrence of white matter abnormalities in the brains of both symptomatic and asymptomatic subjects has been a controversial entity for over a century. The development of magnetic resonance imaging has led to more sensitive detection of these lesions, perhaps even more sensitive than autopsy inspection. More recent clinical studies have determined associations with cognitive decline and gait impairment, and perhaps increased relative risk for cerebrovascular disease. Recently, an animal model of white matter disease and brain atrophy related to diabetes has been established and may assist in the understanding of the pathophysiology of white matter abnormalities. Further clinical and scientific studies will help us understand the importance of white matter abnormalities in the human brain.