A study of Zika virus’s molecular evolution, based on viral strains collected from 4 countries in West Africa during 1947–2007, identified several sites within the Zika viral genome that were under strong negative selection pressure. This finding suggests frequent purging of deleterious polymorphisms in functionally important genes and the possibility of recombination, which occurs rarely among flaviviruses (18). The implications of this finding require further evaluation with respect to viral spread, zoonotic maintenance, and epidemiologic potential.