Ergotamine tartrate (ET) and dihydroergotamine (DHE) are effective therapies for migraine and cluster headache. Optimal management with these agents must take several factors into account, including headache type and severity, associated symptoms, side effect potential, choice of dosage forms, and appropriate dosing. Oral ET is most appropriate for slowly evolving migraine without early onset nausea and/or vomiting, or for treatment of cluster headaches. Delivery of ET via rectal suppository (available only in combination with caffeine) is the most effective form, especially for patients with severe, rapid onset migraine accompanied by nausea and/or vomiting. Dihydroergotamine offers numerous benefits compared to ET, including a lower incidence of nausea and vomiting and headache recurrence, and a lack of rebound headache. Dihydroergotamine can be administered at any time during a migraine attack, including the aura. Intravenous administration provides rapid peak plasma levels and is the most effective form when a rapid effect is desired or for patients with intractable severe headache (status migrainosus, transformed migraine, rebound headache) and cluster headache. Intramuscular administration is effective for moderate to severe migraine with or without nausea and vomiting in the clinic. Intranasal delivery of DHE has shown significant promise for effective and convenient therapy in acute migraine and may be especially useful in the presence of nausea and/or vomiting. When used appropriately, DHE and ET provide clinicians with highly effective therapeutic options in a range of useful dosage forms for patients with migraine or cluster headaches.