White matter was first depicted as a neuroanatomic structure by the great anatomist Andreas Vesalius in 1543. The anatomy of white matter is fundamental to understand its role in brain-behavior relationships. The major function of white matter can be conceived as the transfer of information within the nervous system. The development of magnetic resonance imaging (MRI) in the early 1980s has proven to be a pivotal event in the understanding of white matter and its impact on higher brain function. Ten categories of white matter disorder are: genetic, demyelinative, infectious, inflammatory, toxic, metabolic, vascular, traumatic, neoplastic, and hydrocephalic. Three major groups of syndromes emerge that capture the variety of cognitive and emotional impairments related to cerebral white matter disorders: focal neurobehavioral syndromes, white matter dementia, and neuropsychiatric syndromes. The treatment of cerebral white matter disorders depends on the specific problem disclosed by the diagnostic search.