Prism Adaptation (PA) is a behavioral task to assess visuo-motor plasticity and to ameliorate the symptoms of unilateral spatial neglect. Several studies have addressed the effects of PA on both sensory-motor and cognitive processing and the contribution of different brain regions to PA, although via non standardized procedures. The aim of the present review is to gather findings from the neuro-imaging and neuro-stimulation fields and put forward an interpretative framework for PA. The available evidence supports that sensory-motor effects of PA would mainly relate to the activation of a cerebello-parietal network, while the effects on spatial cognition would be mediated by bottom-up activation of temporal and prefrontal regions. The consolidation of PA effects would rely on activity of the motor cortex. The use of standardized PA procedures is strongly recommended for a systematic and accurate investigation of the neural mechanisms of PA.