Monkeypox has never before appeared more or less simultaneously across different countries and now continents. So this current outbreak is both puzzling and concerning public health workers. Unlike the previous cases discovered outside Africa, the current outbreaks have occurred in people with no travel history, suggesting that human-to-human transmission is driving the spread. And in the current outbreak, the illness appears to be presenting atypically, without its normal prodrome. Read more about the hypothesized connection with smallpox eradication, available vaccinations, and public health response from the outbreak.