The World Health Organization declared the 2022 Monkeypox outbreak as a Public Health Emergency of International Concern, reflecting the rapid spread of infections in non-endemic countries. Since 2022, more than 95,000 confirmed cases with 185 deaths were reported in at least 117 countries, most of them in Europe and USA. Gender-based studies documented preponderance in men (96.8%). Most of them were men who have sex with men (MSM) suggesting the sexual route as the main way of transmission. Mpox infection is usually transmitted by close contact through body fluids, and genital secretions. Exposure to infected respiratory droplets occurs after prolonged exposure. Indirect contact is less frequent. Incubation period is in average 12 days. Prodromal symptoms are systemic and nonspecific succeed with lymphadenopathy. Eruptive rash is changing from macules-papules-blisters-pustules to scabs. Diagnosis is based on clinical occurrence of typical skin and/or mucosal lesions, systemic symptoms, and potential contact to a Mpox-infected individual. The preferred diagnostic test is real-time or conventional polymerase chain reaction (PCR). Laboratory tests based on the detection of antigens or antibodies are not used due to serological cross-reactivity with other orthopoxviruses. The world health authorities agree that smallpox vaccines protect against Mpox infection due to the antigenic similarity between both viruses. New vaccine approved is MVA-BN which contain an attenuated form of vaccinia virus “Ankara” related to the smallpox virus. Antivirals are used to treat Mpox infection, namely cidofovir, tecovirimat and brincidofovir. Individual and universal protective measures should be used to prevent the spread of Mpox viral infection.