A systematic review of the literature on modafinil as adjunctive treatment to antidepressants in patients with major depression and residual symptoms of fatigue and drowsiness is presented. Several open-labelled studies have shown good results on treatment with modafinil. However, only a few randomised controlled clinical trials exist. These have methodological weaknesses and their results are contradictory. If modafinil is used in highly selected patients with severe fatigue its potential interactions with antidepressants must be borne in mind. Furthermore, discontinuation of the drug should be tried after a couple of months, as one study suggests that the effect wears off. In addition, the drug is rather expensive.