The hallmark of menopause is the marked reduction of estradiol levels due to ovarian failure. This, among other factors result in hot flashes, the most common menopausal symptom. Hot flashes (HFs) can be measured objectively, both inside and outside the laboratory, using sternal skin conductance, an electrical measure of sweating. We have found that HFs are triggered by small elevations in core body temperature (T C ), acting within a greatly reduced thermoneutral zone. This reduction is caused by elevated central sympathetic activation, among other factors. There is a circadian rhythm of HFs peaking at 1825 h. Imaging studies have shown that hot flash activation begins in the brainstem, followed by the insula and by the prefrontal cortex. HFs in the first, but not the second half of the night can produce awakenings and arousals. This is because rapid eye movement (REM) sleep suppresses thermoregulatory effector responses, which include hot flashes.