Migraine is a common episodic headache disorder. A comprehensive headache treatment plan includes acute attack treatment to relieve pain and impairment and long-term preventive therapy to reduce attack frequency, severity, and duration. Circumstances that might warrant preventive treatment include: (i) migraine that significantly interferes with the patient's daily routine despite acute treatment; (ii) failure, contraindication to, or troublesome side-effects from acute medications; (iii) overuse of acute medications; (iv) special circumstances, such as hemiplegic migraine; (v) very frequent headaches (more than two a week); or (vi) patient preference. Start the drug at a low dose. Give each treatment an adequate trial. Avoid interfering, overused, and contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing potential is aware of any potential risks. Involve patients in their care to maximize compliance. Consider co-morbidity. Choose a drug based on its proven efficacy, the patient's preferences and headache profile, the drug's side-effects, and the presence or absence of coexisting or co-morbid disease. Drugs that have documented high efficacy and mild to moderate adverse events (AEs) include β-blockers, amitriptyline, and divalproex. Drugs that have lower documented efficacy and mild to moderate AEs include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate, riboflavin, and non-steroidal anti-inflammatory drugs.