Cognitive impairment occurs in 40–70% of patients with multiple sclerosis (MS). It is observed even at the early stage of disease, including clinically isolated syndrome (CIS). Cognitive dysfunction develops irrespectively of the physical disability. Affected domains include: information processing speed, visuospatial abilities, attention, verbal memory and executive functions. Cognitive deficits have relevant implication because of their impact on daily living, quality of life and increased risk of conversion from CIS to MS. In the recent years the issue of cognitive impairment in MS became an important research problem. The fundamental aim is to understand the neurobiological substrates of these mental symptoms. As we know neurodegenerative process associated with the disease, pathology of cerebral cortex and damage to the normal appearing brain tissue are potentially involved in the development of cognitive symptoms. Better assessment of these cerebral changes is possible through the improvement of magnetic resonance imaging techniques. Influence of genetic profile on the course of MS, including cognitive dysfunction, is still under evaluation. Despite using the new neuroimaging methods, the substrate of cognitive impairment in MS has not been clearly defined so far. Understanding the mechanisms underlying cognitive symptoms may extend our knowledge of the pathophysiology of the disease and also contribute to the development of new strategies and objectives for treatment. This paper provides a summary of the results obtained from the application of conventional and modern magnetic resonance imaging techniques to assess structural pathologies occurring in MS as well as genetic factors and their association with cognitive dysfunction.