Alan Rapoport discusses the challenges associated with diagnosis and treatment of migraine. Although there are several signs and symptoms suggestive of migraine, there are also many migraine mimics. Diagnosis and treatment of comorbidities, such as depression and anxiety are also key to treating the patient optimally. Preventive treatment may help a large proportion of patients, but is suboptimally used, and may have side effects, such as weight gain and drowsiness. There is a real unmet need for preventive medications that work for a larger percentage of patients, without the side effects associated with current treatments.