Fatigue is a common and potentially debilitating symptom of amyotrophic lateral sclerosis (ALS). Questionnaire studies show that ALS subjects have increased subjective fatigue. Physiologic studies demonstrate that ALS subjects have increased physical fatigue, both central and peripheral in origin. No treatment has been proved effective through evidence-based medicine; however, modafinil (Provigil) may be a helpful pharmacologic treatment. Palliative care measures, such as noninvasive ventilation and high-frequency chest wall oscillation, may also reduce fatigue.