Fatigue is a common symptom in neurology and occurs in the diseases of the central and peripheral nervous system. In order to understand the mechanism of fatigue, it is important to distinguish symptoms of peripheral neuromuscular fatigue from the symptoms of physical and mental fatigue characteristic of disorders like Parkinson's disease or multiple sclerosis. We have introduced and defined the concept of central fatigue for the latter disorders. We have further proposed, with supportive neuropathological data, that central fatigue may occur due to a failure in the integration of the limbic input and the motor functions within the basal ganglia affecting the striatal-thalamic-frontal cortical system.