Depending on their frequency and severity, hot flashes can be a major source of distress for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Characterized by increased skin temperature, skin conductance, and heart rate, hot flashes are associated with somatic, behavioral, and emotional manifestations. In this article, the authors review the prevailing theories on the pathophysiology of hot flashes and assess the major treatment interventions, such as hormonal agents, nonhormonal pharmacotherapy (including antidepressants), and complementary/alternative medicine options.