Migraine is a neurovascular syndrome characterized by recurrent headache associated with other symptoms, eventually preceded by aura. This chapter reviews the involvement of some mineral, coenzyme, and vitamin defects in the pathogenesis of migraine headaches and focuses on their potential therapeutic use in the preventive treatment for migraine. The therapeutic potential of magnesium, coenzyme Q(10), riboflavin, and vitamin B(12) can be cautiously inferred from some published open clinical trials; it should, however, be considered that double-blind randomized larger studies are needed to correctly estimate the impact of the placebo effect in these promising therapies.