Cognitive impairments in multiple sclerosis (MS) are heterogeneous and their rate varies between 43% and 70%. A less studied aspect of cognition is social cognition, which is not a uniform theoretical construct. It includes emotion perception, prosody, empathy, theory of mind (ToM) and assessment of mood. In addition to progressive physical disability, social cognitive impairments are a reason for job loss in 24-80% of patients with MS, increased divorce rate, dissolution of partnerships and social communication difficulties.Social cognitive impairments are the result of disruptions in the mentalization network at the neuroanatomical, neurochemical and/or genetic level, which can lead to malfunctions in the dopaminergic-serotoninergic system and to compromising the development of neuroanatomical targets within the network. The wide dissemination of demyelinating lesions and cortical thinning typical of patients with MS often lead to anatomic and functional disorders of the above-mentioned specific brain structures. A correlation has been established among specific cortical areas involved in emotion identification from facial expression (right and left fusiform face area, frontal eye), emotion processing (right entorhinal cortex) and socially relevant information (left temporal pole). The most active brain region involved in social cognitive processing is the medal frontal cortex (MFC), which is described as the brain's social cognitive center. During performance of various sociocognitive tasks for mental state attribution, common areas of increased activation in the medial prefrontal gyrus and the temporoparietal junctions are registered bilaterally, while the area of the medial prefrontal cortex (the paracingulate cortex) is the only region uniquely activated by the performance of ToM.Most MRI studies of patients with MS found a correlation between the cognitive and/or affective disorders, on the one hand, and lesion localization, total lesion load, or cerebral atrophy, on the other. A significant correlation was also reported between © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.abnormal activities in specific cortical zones on fMRI, on the one hand, and clinical manifestation, conventional MRI findings and behavioral changes, on the other. Altered patterns of brain activity were found in all clinical phenotypes of MS, including when cognitive abilities were intact and/or restored, social cognitive dysfunction in MS actually affects all stages of the disease and all types of clinical course. The cortical plastic changes are a dynamic phenomenon that can be modulated by external factors. This phenomenon would facilitate the mapping of individual strategies for adequate treatment and rehabilitation of each patient.