Emerging and reemerging infections have become prevalent in the United States since the 1970s, causing illness, death, and fear among the public. The published literature was reviewed to offer a perspective on risk factors for disease acquisition and to allow a prediction of the next microbial assault after Ebola and Zika. Four well-integrated factors likely will contribute simultaneously: animals colonized or infected by pathogens capable of human transmission, microbes recurrently changing their virulence, a growing number of susceptible people, and climatic and environmental factors encouraging disease transmission. The next pathogen likely to emerge in an important way in the United States is a new mutant virus arising from a well-established RNA virus family. Standard public health principles, including monitoring general populations for disease, developing new reagents as pathogens arise, implementing control efforts such as effective antibiotic stewardship programs, and vaccine development and administration will minimize damage from the emerging organisms.