Persistent cognitive disabilities represent the most troublesome consequences of acquired brain injury. Although these problems are widely recognized, few neuroprosthetic efforts have focused on developing therapeutic strategies aimed at improving general cognitive functions such as sustained attention, intention, working memory or awareness. If possible, effective modulation of these neuropsychologic components might improve recovery of interactive behaviors. The emerging field of neuromodulation holds promise that technologies developed to treat other neurological disorders may be adapted to address the cognitive problems of patients suffering from acquired brain injuries. We here discuss initial efforts at neuromodulation in patients in the persistent vegetative state and aspects of recent studies of the underlying neurobiology of PVS and other severe brain injuries. Innovative strategies for open-loop and closed-loop neuromodulation of impaired cognitive function are outlined. We discuss the possibilities of linking neuromodulation techniques to underlying neuronal mechanisms underpinning cognitive rehabilitation maneuvers. Ethical considerations surrounding the development of these strategies are reviewed.