Vasomotor symptoms (VMS), commonly called hot flashes or flushes (HFs) and night sweats, are the menopausal symptoms for which women seek treatment during menopause most often. VMS are a form of temperature dysfunction that occurs due to changes in gonadal hormones. Normally, core body temperature (CBT) remains within a specific range, oscillating with daily circadian rhythms. Physiological processes that conserve and dissipate heat are responsible for maintaining CBT, and tight regulation is important for maintenance of optimal internal organ function. Disruption of this tightly controlled temperature circuit results in exaggerated heat-loss responses and presents as VMS. The mechanistic role related to changes in gonadal hormones associated with VMS is not understood. Hormone therapy is the most effective treatment for VMS and other menopausal symptoms. Estrogens are known potent neuromodulators of numerous neuronal circuits throughout the central nervous system. Changing estrogen levels during menopause may impact multiple components involved in maintaining temperature homeostasis. Understanding the pathways and mechanisms involved in temperature regulation, probable causes of thermoregulatory dysfunction, and "brain adaptation" will guide drug discovery efforts. This review considers the processes and pathways involved in normal temperature regulation and the impact of fluctuating and declining hormones that result in VMS during the menopausal transition.