Headache disorders can be further classified as episodic (< 15 headache days per month) or chronic (≥15 headache days per month for more than 3 months). Chronic migraine (CM) requires that headaches occur on 15 or more days a month for more than 3 months. These headaches must be migraines on at least 8 days per month. There are seven botulinum toxin (BoNT) serotypes (A1, A2, A3, B, C1, D, E, F, and G). All serotypes inhibit acetylcholine release, although their intracellular target proteins, physiochemical characteristics, and potencies are different. Its mechanism of action in pain is being investigated. Botulinum toxin type A (BoNT-A) has been the most widely studied serotype for therapeutic purposes. A major clinical advantage of type A toxin arises from its prolonged duration of action due to the longevity of its protease (90 days in rats and probably much longer in human neurons). Clinical studies suggest that BoNT is a safe treatment and is efficacious for the prevention of some forms of migraine, such as CM, and perhaps high-frequency episodic migraine.