PURPOSE OF REVIEW: Basic and translational neuroscience findings indicate that normal brain function depends on activity synchronization within distributed brain networks. This conclusion suggests a view of how brain injury causes behavioral deficits that differs from traditional localizationist views. RECENT FINDINGS: Novel functional neuroimaging methods demonstrate coherent activity in large-scale networks not only during task performance but also, surprisingly, at rest (i.e. in the absence of stimuli, tasks, or overt responses). Furthermore, breakdown of activity coherence at rest, even in regions of the brain that are structurally intact, correlates with behavioral deficits and their recovery after injury. Breakdown of functional connectivity appears to occur not just after local injury but also in other conditions that affect large-scale neural communication. SUMMARY: A network perspective is fundamental to appreciating the pathophysiology of brain injury at the systems level and the underlying mechanisms of recovery, and for developing novel strategies of rehabilitation.