Hot flashes are prevalent and severe symptoms that can interfere with mood, sleep, and quality of life for women and men with cancer. The purpose of this article is to review existing literature on the risk factors, pathophysiology, and treatment of hot flashes in individuals with cancer. Electronic searches were conducted to identify relevant English-language literature published through June 15, 2012. Results indicated that risk factors for hot flashes in cancer include patient-related factors (eg, age, race/ethnicity, educational level, smoking history, cardiovascular risk including body mass index, and genetics) and disease-related factors (eg, cancer diagnosis and dose/type of treatment). In addition, although the pathophysiology of hot flashes has remained elusive, these symptoms are likely attributable to disruptions in thermoregulation and neurochemicals. Therapies that have been offered or tested fall into 4 broad categories: pharmacological, nutraceutical, surgical, and complementary/behavioral strategies. The evidence base for this broad range of therapies varies, with some treatments not yet having been fully tested or showing equivocal results. The evidence base surrounding all therapies is evaluated to enhance hot flash treatment decision-making by clinicians and patients. CA Cancer J Clin 2013. © 2013 American Cancer Society.