OBJECTIVE The purpose of this paper is to review and synthesize current literature in which neurochemical and structural brain imaging were used to investigate chronic migraine (CM) pathophysiology and to further discuss the clinical implications. RESULTS Spectroscopic and structural MRI studies have shown the presence of both impaired metabolism and structural alterations in the brain of CM patients. Metabolic changes in key brain regions support the notion of altered energetics and homeostasis as part of CM pathophysiology. Furthermore, CM, like other chronic pain disorders, may undergo structural reorganization in pain-related brain regions following near persistent endogenous painful input. Finally, both imaging techniques may provide potential biomarkers of disease state and progression and may help guide novel therapeutic interventions or strategies. Spectroscopic and structural MRI have revealed novel aspects of CM pathophysiology. Findings from the former support the metabolic theory of migraine pathogenesis.