Multiple sclerosis (MS) is a common neurological disease in the Western hemisphere that leads to neurological dysfunctions and frequently from its onset to cognitive impairment, which together predict quality of life. Recent pathological and imaging studies have focused on brain atrophy representing axonal injury and loss as being crucial for developing disability and neuropsychological impairment. Brain atrophy has therefore been proposed to be a tool for monitoring disease progress. Here, we review the possible origins of brain atrophy and its correlation with cognitive impairment in MS.