Migraine and fibromyalgia are prevalent and disabling disorders with few preventive medications approved by the US Food and Drug Administration (FDA). Neuromodulators (or antiepileptic drugs; AEDs) are often effective in the treatment of these conditions. Divalproex sodium and topiramate are FDA-approved AEDs for migraine. For fibromyalgia, pregabalin has recently been approved in the United States. We review the use of AEDs in the preventive treatment of these highly prevalent disorders.