Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS) patients. This symptom's etiopathogenic mechanism, though not known, seems complex and multifactorial, and its therapeutic management is difficult. Different treatments have been tested in recent years, but a weak efficacy that may be limited in time has been observed. Recently, modafinil has been suggested as a possible treatment for fatigue in MS patients, although nowadays, the only use of modafinil approved by the Food and Drug Administration is narcolepsy. Modafinil, 2-([difenilmetil]sulfinil), acetamide is a state of wakeness promoter, and although its exact action mechanism is not known, it differs from other central nervous system stimulants because no dopaminergic activation is observed, and its action take place at the hypothalamic level. It is known that modafinil increases the proportion of high-frequency alpha waves and reduces delta and theta waves, increasing vigilance. Although few studies exist on modafinil in MS patients with fatigue, the results suggest this drug as a promising treatment, because of its efficacy and safety, and should encourage us to continue working in this area.