The current monkeypox (MPX) outbreak has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). It is a zoonotic disease that has persisted in the African basin for decades but suddenly exploded into the international sphere this year. In this paper, we provide a comprehensive overview of monkeypox, including a hypothesis of the rapid spread of the virus, its epidemiology and clinical features, a comparison with other orthopoxviruses such as chickenpox and smallpox, past and present outbreaks, and strategies for its prevention and treatment.