Among women with breast cancer, hot flashes are a frequent, severe and bothersome symptom. For this group, hot flashes are negatively related to mood, affect, and daily activities and can compromise compliance with life-saving medications (e.g., tamoxifen). Over 60% of breast cancer survivors report hot flashes, with 59% stating they are extremely severe and 44% reporting them to be extremely bothersome. Unfortunately, limitations in our understanding of hot flash physiology limit clinicians' abilities to fully treat this symptom. Although the current non-hormonal treatment of choice for hot flashes after breast cancer targets the central serotonin system (e.g., paroxetine, venlafaxine), the role of serotonin in hot flashes has not been directly tested. Because the effectiveness of these agents has been based largely on improvement in subjective reporting of hot flashes, it is not clear whether benefits are due to physiological effects on hot flashes or due to improvements in mood or other related symptoms. In addition, these and other currently available treatments are not acceptable, appropriate, or effective for all women with breast cancer. Understanding the physiological mechanisms involved in hot flashes after breast cancer will enable us to develop more targeted behavioral and/or pharmacological therapies to be used in lieu of, or in addition to, currently available therapies so that we can eradicate hot flashes and improve the quality of life for women with breast cancer.