Following the eradication of smallpox, intermittent small outbreaks of mpox (monkeypox) have occurred with increasing frequency, primarily in endemic regions of Africa. With the rapid spread of mpox around the globe in 2022, we are approaching a second zoonotic pandemic of the 21st century. Given the predominance of cutaneous involvement in mpox, dermatologists should be prepared to recognize the clinical features and manage this increasingly prevalent disease. This article reviews a brief history of the mpox virus, clinical presentation, complications, approach to diagnosis, methods of transmission, infection control recommendations, indications for vaccination, and therapeutic options to inform dermatologists on the frontline of the mpox epidemic.