Fatigue may be defined as a subjective lack of energy or feeling of exhaustion. In about 70% of cases fatigue is among three most disabling MS symptoms, and in part of patients the most severe symptom. Fatigue may be general or focal. Fatigue is made worse by stress, depression, prolonged physical activity and heat, having important impact on day-to-day activity, family and social life. Improvement is observed after resting and sleeping. There is an association between fatigue in MS patients and dysfunction of frontal cortex and basal ganglia. In the pathogenesis immune factors and changes in neutrotransmission play also a role. In pharmacological treatment positive effects were achieved with amantadine, modafinil, antidepressive drugs. Improvement was noticed after rehabilitation, psychotherapy and emotional support.