Background: Yellow fever virus (YFV) is an RNA virus maintained in an enzootic, sylvatic cycle involving nonhuman primates (NHPs) and sylvatic mosquito vectors primarily of the genus Haemagogus and Sabethes. Transmission occasionally spills over to humans entering forested regions. In the Americas, urban transmission of YFV to humans has not occurred since the mid-1900s because of vaccination and near-elimination of the anthropophilic Aedes aegypti, the urban vector (1). However, concerns about reemergence of urban YFV have recently increased because of the reappearance and rapid spread of A aegypti in the urban environment. Furthermore, immunization coverage for YFV is insufficient because vaccination is generally indicated only for higher-risk populations, such as those living in or travelling to areas with sylvatic transmission. Objective: To investigate the 2017 epizootic outbreak of YFV and the risk for human disease in Salvador, Brazil. Methods and Findings: Since November 2016, deaths of NHPs due to YFV in Brazil have been reported in the state of Sa˜o Paulo. Beginning in December 2016, human cases were also reported in the states of Sa˜o Paulo and Minas Gerais. By the end of May 2017, the YFV outbreak in humans had spread to 9 Brazilian states, with more than 130 municipalities reporting confirmed cases (Appendix Figure 1, available at www .annals.org), all deemed of sylvatic origin (rather than via urban A aegypti transmission).