Nutrition must affect the structure and functioning of the brain. Since the brain has very high metabolic activity, what we consume throughout the day is likely to dramatically influence both its structure and moment to moment function. It follows that nutritional approaches to all neurological disorders are being researched and entering medical practice, while nutraceutical use is a mainstay of public habits. This review discusses the biological basis for non-conventional or non-mainstream approaches to the treatment of migraine. This requires at least limited discussion of current migraine pathophysiologic theory. How nutrients and other chemicals and approaches are mechanistically involved within migraine pathways is the focus of this article. The nutraceuticals reviewed in detail are: magnesium, riboflavin, coenzyme Q10, petasites, and feverfew with additional comments on marijuana and oxygen/hyperbaric oxygen. This article reviews the science when known related to the potential genetic susceptibility and sensitivity to these treatments. As we know, the basic science in this field is very preliminary, so whether to combine approaches and presumably mechanisms or use them alone or with or without conventional therapies is far from clear. Nonetheless, as more patients and providers participate in patient-centered approaches to care, knowledge of the science underpinning nutritional, nutraceutical, and complementary approaches to treatment for migraine will certainly benefit this interaction.