Zika virus has the propensity to infect large numbers of persons with severe consequences in some cases. The epidemic has serious medical, ethical, and economic ramifications, particularly in countries where the resources for early diagnosis are lacking and potential intervention measures are discouraged or illegal. Although autochthonous transmission in the United States is unlikely to match the scale of the epidemic in Central and South America, much about Zika virus and the way the pandemic will evolve are unknown. Continued vigilance is warranted, along with a concerted effort toward improving our understanding, management, and prevention of this emerging pathogen.