Drugs such as modafinil (an agent promoting wakefulness) are used to try to counteract the fatigue of multiple sclerosis (MS), but evidence for their efficacy is scant. A randomised, placebo controlled, double blind study of modafinil including 115 patients found no improvement after five weeks ( Neurology 2005;64: 1139-43[Abstract/Free Full Text]), although a randomised controlled crossover trial of aspirin in 30 patients with MS published in the same issue (1267-9) shows that the drug alleviated the problem. The authors propose that aspirin may work by blocking the output of the hypothalamus, which in turn affects the neuroendocrine and autonomic responses important in the perception of fatigue.