Botulinum toxin type A (BoNT-A) has long been used to treat disorders associated with increased muscle tone. Support for an analgesic effect of BoNT-A independent of its muscle relaxation effect came from clinical observations that some patients with dystonia obtained pain relief before they obtained improvement in muscle tone.1 Injections of BoNT-A were discovered serendipitously to alleviate migraine headache when they were given for the treatment of facial wrinkles.2 After several open-label studies showed that BoNT-A might have efficacy in headache treatment, randomized controlled trials were initiated to investigate this issue further.3 New scientific data have provided insight into mechanisms by which BoNT-A may exert its analgesic effect. In our discussion, we focus on clinical data obtained from randomized controlled trials.