Cluster headache needs to be rapidly diagnosed and effectively managed, as the individual headache attacks that are characteristic of this disorder are excruciatingly painful and debilitating. Preventive therapies are necessary to reduce the frequency of attacks during the cluster period. However, preventive therapy for this disorder is limited by a lack of controlled evidence of efficacy and the potential for systemic toxicity. Recent progress has been made in understanding both the pathophysiological mechanisms underlying cluster headache and the mechanisms of action of the antiepileptic drug class for the treatment of primary headache syndromes. Newly available preliminary clinical trial data evaluating antiepileptic drugs for the prevention of cluster headache suggest that these agents may be effective and that further evaluation in randomized, placebo-controlled trials is warranted.