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When we engage in social interaction with others, we constantly share and infer their emotion, belief, and thought. Thus, social cognitions such as emotion recognition and mind-reading play a crucial in successful interpersonal relationship. It has been demonstrated that social brain including the amygdale, anterior cingulated cortex, insula, orbitofrontal cortex and medial prefrontal cortex are activated in association with social cognition. In fact, social cognition deficits have been reported in a variety of neuropsychiatric disorders, for example, autistic spectrum disorder, patients with frontal lobe damage, and schizophrenia. Recently, several studies revealed that substance abusers showed the impairments in social cognition and alterations in neural correlates relevant to it. Thus, social cognition deficits and altered neural networks related to it in substance abusers may lead to misunderstandings and impairment of interpersonal communication, which could in turn contribute to hostility and stress during interpersonal relationship. These alterations in socio-emotional behaviors might be related to relapse and sustainment of substance abuse. Therefore, treatment and rehabilitation for substance abusers must consider the role of social cognition and include relearning of social interactions and behaviors.