Fatigue is one of the most common symptoms of multiple sclerosis (MS), and it can have a major impact on health-related quality of life. Therefore, it is imperative that healthcare practitioners regularly assess fatigue in their patients with MS. Fatigue can be caused either by the disease process (primary fatigue) or by other problems such as insomnia, infections, or depression (secondary fatigue). Because the causes of secondary fatigue are generally amenable to treatment, it is important that healthcare practitioners distinguish between the two types of fatigue when assessing and treating fatigue. Because fatigue is a subjective experience, it can be difficult to measure. Tools such as the Fatigue Impact Scale and the Fatigue Severity Scale can be used to help clinicians and researchers measure fatigue. The Symptom Management Model can be used to guide healthcare practitioners in the assessment and treatment of fatigue. A variety of treatment options are available for MS-related fatigue, and it is important that patients and their support systems are made aware that fatigue can be managed.