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Multiple Sclerosis (M.S) is one of the prevalent diseases of the central nervous system which cause disability in young adults. This appears as neural signs in different parts and various times. The main defect is local deterioration or destruction of myelin tissue in the brain and spinal cord. Profound fatigue is one the most common symptoms of this disease. Because MS is prevalent in middle ages, so the presence of this symptom affects the life and activity of the patient In these ages people have high amount of activities and this functional disorder creates many difficulties for daily works in patient. For this reason, fatigue problem in patients, always, have caught the attention of researchers. Despite numerous studies, still the exact reason for producing fatigue have not been mentioned But several mechanisms have been discussed, such as: autoimmune mechanism of the disease, Involvement and disorder of endocrine system, involvement of central nervous system and de-synchronization of autonom system. Among these, autoimmune mechanism is considered as a main role in producing fatigue. Lack of proper knowledge regarding exact fatigue mechanism several problems in its treatment. Evaluation is the first step for controlling fatigue, which is done through various tests. Clear and proper evaluation can be obtained by these tests. After evaluation, non-drug and finally drug procedures are helpful. In non-drug treatment the focus is on: sport exercises, suitable diet program, identification and improvement of the patient psychotic disorders, energy conservation methods. Finally, the use of drugs such as Amantadine, Pemoline and Modafini is recommended for fatigue treatment.