The global vaccination programme against smallpox (SPX) led to its successful eradication and averted millions of deaths. Monkeypox (MPX) is a close relative of SPX. Due to their antigenic similarity, SPX vaccines cross-protect against MPX. However, over 70% of people living today were never vaccinated. Symptoms of MPX infection include fever, head and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from less than 1% to up to 11%) than SPX (up to 30%). MPX is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel combined with the increasing susceptibility of the human population due to halted vaccination facilitated the spread of MPX to new areas. The ongoing outbreak with over 6500 confirmed cases in >50 countries between May and July 2022 shows that MPX can significantly spread between people, and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population.