Disorders of flushing encompass a broad spectrum of diverse acquired and inherited conditions. Chemical mediators involved in the flushing response are incompletely understood. Flushing episodes rarely can be associated with significant morbidity and mortality. The goal of the physician is to separate benign from potentially life-threatening conditions. Accurate diagnosis requires a thorough history and physical examination emphasizing the age of the patient, temporal association of flushing with occupation, environmental, stress, food, or drug exposure, and the duration of the episode. In some cases, despite a thorough evaluation, the etiology for flushing remains unknown. Understanding the distinct mechanisms that lead to flushing helps provide a rational approach to treatment.