Social isolation may be considered as a risk factor for health. It may contribute to the development of a mental health disease. In this chapter, social withdrawal is defined as voluntary isolation prolonged in time that involves the cessation of any form of social relationship and contact with people and the outside. Clinical psychology, psycho-educational interventions, and social neuroscience research tries to understand what happens when social isolation is experienced. Therefore an interdisciplinary perspective can help to better understand this phenomenon. The deepening of these aspects can help to create new forms of theoretical perspective and of a clinical and psycho-educational intervention to better arrange for this new type of maladaptive condition.