Cluster headache pain is very intense, usually increases in intensity very rapidly from onset, and attacks are often frequent. These clinical features result in significant therapeutic challenges. The most effective pharmacological treatment options for acute cluster attack include subcutaneous sumatriptan, 100% oxygen, and intranasal zolmitriptan. Subcutaneous or intramuscular dihydroergotamine and intranasal sumatriptan are additional options. Transitional therapy is applicable mainly for patients with high-frequency (>2 attacks per day) episodic cluster headache, and options include short courses of high-dose oral corticosteroids, dihydroergotamine, and occipital nerve blocks with local anesthetic and steroids. Prophylactic therapy is important both for episodic and chronic cluster headache, and the main options are verapamil and lithium. Verapamil is drug of first choice but may cause cardiac arrhythmias, and periodic electrocardiograms (EKGs) during dose escalation are important. Many other drugs are also in current use, but there is an insufficient evidence base to recommend them.