Modern theories of brain function emphasize the importance of distributed functional networks and synchronized activity within and between networks in mediating cognitive functions. This view highlights the importance of considering brain-behavior relationships after focsal lesions not only as the result of local structural damage but also as a more widespread alteration of the physiological state of networks connected to the lesion. Recent findings demonstrate coherent activity in large-scale brain networks not only during task performance, but also, surprisingly, at rest in the absence of stimuli, tasks, or overt responses. Moreover, breakdown of coherent activity at rest, even in regions that are structurally intact, correlates with behavioral deficits and with their recovery after injury. This network perspective is fundamental to understand not only healthy brain function, but also the pathophysiology of brain injuries, mechanisms of functional recovery, and the basis for novel interventions for therapy. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 54:239-253, 2012.