A recent research demonstrated an impaired brain metabolism in chronic migraine patients with medication overuse headache. Besides other findings, reduced total creatine levels have been found in the left thalamus of 32 chronic migraine patients with and without medication. A brain creatine deficiency found is highly suggestive of altered energy homeostasis in chronic migraine, a phenomenon already identified in a secondary headache, where patients with semi-acute mild traumatic brain injury experienced higher creatine levels in the white matter and splenium, perhaps signaling a higher creatine turnover in the mildly compromised brain as a compensatory response in the face of the increased needs. The question that inevitably arises is could the low brain creatine be a new biological target for therapeutics (including exogenous creatine) in chronic migraines? We tried to address this in a letter recently published in Cephalalgia!