Almost every woman and some men will encounter hot flushes during their lifetime. Despite the prevalence of the symptoms, the pathophysiology of hot flushes remains unknown. A decline in hormone concentrations might lead to alterations in brain neurotransmitters and to instability in the hypothalamic thermoregulatory setpoint. The most effective treatments for hot flushes include oestrogens and progestagens. However, many women and their physicians are reluctant to accept hormonal treatments. Women want non-pharmacological treatments but unfortunately such treatments are not very effective, and non-hormonal drugs are often associated with adverse effects. Results from recent studies showed that selective serotonin reuptake inhibitors and other similar compounds can safely reduce hot flushes. Moreover, the efficacy of these drugs provides new insight into the pathophysiology of hot flushes. In this critical review, we assess knowledge of the epidemiology, pathophysiology, and treatment of hot flushes.