Over the past four decades, it was found that folic acid supplementation produced an antidepressant-like effect mediated by interaction with the brain noradrenergic receptors (inhibitory effect) and serotonergic receptors (stimulatory effect). Hot flushes occur in postmenopausal women because of disturbances in the thermoregulatory centre, most likely as a result of estrogen deficiency-related increase in central noradrenergic activity and reduced serotonergic activity. Therefore, we hypothesize that folic acid supplementation may ameliorate hot flushes by the same mechanism as estrogen replacement, i.e., by interacting with monoamine neurotransmitters in the brain; namely norepinephrine and serotonin. This article discusses the hypothesis and presents supportive preliminary data.