Migraine headaches are a debilitating condition that affects approximately 1% of the US population. Goals of migraine prophylaxis include reduction in headache severity and frequency, improved response to acute treatment, fewer days with disability, improvement in quality of life, and empowerment of patients with a sense of control over the condition. Indications for consideration of preventive therapy include frequent headaches, failure of or contraindication to acute treatments, overuse of acute treatments, and patient preference. First-line medications include propranolol, metoprolol, topiramate, divalproex, valproate, and calcitonin gene–related peptide receptor antagonists. However, use of calcitonin gene–related peptide receptor antagonists is limited by cost and insurance coverage. Amitriptyline and venlafaxine are considered second-line medications due to a greater number of adverse events and less supporting evidence, respectively. OnabotulinumtoxinA (Botox) injection is approved for chronic migraine prophylaxis. It is as effective as other medications, is well tolerated, and has lower discontinuation rates than other drugs. Common migraine triggers include alcohol, anxiety, dehydration, excessive caffeine, eye strain, hunger, sleep deprivation, and stress. Physicians should recommend identification and management of migraine triggers. Cognitive behavior therapy, acupuncture, neural stimulators, and exercise are supported by varying levels of evidence and can be used individually or in combination with pharmacotherapy. Alternative agents, including feverfew, magnesium, and melatonin, have shown effectiveness and are generally well tolerated.