Many women experience vasomotor symptoms at or around the time of menopause. Hot flushes and night sweats are considered primary menopausal symptoms that may also be associated with sleep and mood disturbances, as well as decreased cognitive function. All of these symptoms may lead to social impairment and work-related difficulties that significantly decrease overall quality of life. Hot flushes have shown a great deal of variability in their frequency and severity in women. In some women, hot flushes persist for several months; in others, they may last for more than 10 years. Traditionally vasomotor symptoms were reported to begin 5 to 10 years prior to the cessation of the final menstrual cycle, corresponding with the initial decline in circulating gonadal hormones; however, night sweats in particular most often begin in perimenopause. The pathogenesis of hot flushes has not yet been fully elucidated, but the circuitry involving estrogen and neurotransmitters, norepinephrine and serotonin specifically, are hypothesized to play a major role in the altered homeostatic thermoregulatory mechanisms underlying these events. Menopause-associated vasomotor symptoms are associated with significant direct and indirect costs. Overall costs of traditional pharmacotherapy or complementary and alternative medicine modalities, including over-the-counter treatments and dietary supplements, for managing menopause-related vasomotor symptoms are substantial and include initial and follow-up physician visits and telephone calls. Additional costs include laboratory testing, management of adverse events, loss of productivity at work, and personal and miscellaneous costs. Pharmacoeconomic analyses, including those that consider risks identified by the Women's Health Initiative, generally support the cost-effectiveness of hormonal therapy for menopause-associated vasomotor symptoms, which have been the mainstay for the management of these symptoms for more than 50 years. However, because many women now want to avoid hormone therapy, there is a need for additional targeted therapies, validated by results from controlled clinical trials that are safe, efficacious, cost-effective, and well tolerated by symptomatic menopausal women.