Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction, including cervical dystonia, blepharospasm and hemifacial spasm. It inhibits neurouscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient with normal neuronal signaling returning within approximately 3-6 months post injection. Recently, clinical findings suggest that BoNT/A may inhibit pain associated with migraine and other headache types. The mechanism by which this toxin inhibits pain is under investigation, recent findings suggest that it inhibits the release of neurotransmitters from nociceptive nerve terminals and in this way may exert an analgesic effect. A number of retrospective open-label chart reviews and three placebo-controlled double-blind trials have demonstrated that localized injections of BTX-A significantly reduce migraine frequency, severity, and migraine-associated disability. The majority of patients in these studies experienced no BoNT/A mediated side effects; however, a small percentage of patients did report transient minor side effects including blepharoptosis, dipolpia, and injection-site weakness. Currently there are several large-scale randomized, placebo-controlled clinical trials in progress evaluating the efficacy, optimal dosing and side effect profile of this toxin as a novel treatment for migraine and other headache types. These studies may provide further evidence that BoNT/A is an effective option for the preventive treatment of migraine.