Since May 2022, monkeypox (MPX) cases have been reported from several European countries, and this outbreak rapidly spread globally. Although MPX is not a new disease, most clinicians in nonendemic countries are unfamiliar with it. In addition, this current outbreak, unlike previous outbreaks in Africa, shows unique features in terms of epidemiology, transmission routes, and clinical manifestation. Most cases were men who have sex with men, had no travel history to an MPX endemic area, and presented with anogenital lesions, suggesting human-to-human transmission via close contact during sexual activity. In the emergency department setting, rapid identification of suspected cases and implementation of effective infection control and preventive measures are critical for preventing further transmission to healthcare workers and other patients. Emergency department clinicians should be aware of the clinical presentations of MPX and be alert to patients presenting with fever and vesicular rash or sexually transmitted disease-associated rash, especially among those with travel history to countries reporting an MPX outbreak. This brief review provides current information of MPX to help emergency department clinicians understand the epidemiology, transmission, clinical manifestation, diagnosis, treatment, and infection prevention and control of MPX.