Fatigue is an extremely prevalent issue for multiple sclerosis (MS) patients. Fatigue can affect quality of life, depression, anxiety, motor function and sleep patterns. There are a number of available rating scales designed to detect and assess fatigue. However, the pathophysiology of fatigue is still not completely understood and the treatment of this symptom remains difficult. A number of clinical trials for fatigue in MS have shown some benefit with different interventions, including medication, physical activity and cognitive-behavioral therapy. Nonetheless, further research and the development of more targeted therapies are needed to improve the management of fatigue.