Unilateral spatial neglect is a disabling neurological condition that typically results from right hemisphere damage. Neglect patients are unable to take into account information coming from the left side of space. The study of neglect is important for understanding the brain mechanisms of spatial cognition, but its anatomical correlates are currently the object of intense debate. We propose a reappraisal of the contribution of disconnection factors to the pathophysiology of neglect based on a review of animal and patient studies. These indicate that damage to the long-range white matter pathways connecting parietal and frontal areas within the right hemisphere may constitute a crucial antecedent of neglect. Thus, neglect would not result from the dysfunction of a single cortical region but from the disruption of large networks made up of distant cortical regions. In this perspective, we also reexamined the possible contribution to neglect of interhemispheric disconnection. The reviewed evidence, often present in previous studies but frequently overlooked, is consistent with the existence of distributed cortical networks for orienting of attention in the normal brain, has implications for theories of neglect and normal spatial processing, opens perspectives for research on brain–behavior relationships, and suggests new possibilities for patient diagnosis and rehabilitation.