Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies considerably among subjects. The dose of verapamil used for cluster headache is approximately double the dose used in cardiovascular disease, most likely because verapamil is a substrate for the efflux transporter P-glycoprotein in the blood–brain barrier. The access of verapamil to the central nervous system is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus.Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca2+ channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain mode of action of the drug in cluster headache.