Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is related to other pathogens of clinical importance, including yellow fever and dengue (DENV) viruses. Although once infrequently associated with human disease, ZIKV has emerged as a global health threat with its introduction into South America during 2014 and 2015. Of concern, recent ZIKV outbreaks are linked to severe neuro-developmental complications in the children of women infected while pregnant, as well as Guillain-Barré syndrome in adults (1). Management of this epidemic has been complicated by extensive serological cross-reactivity among flaviviruses and the cocirculation of ZIKV and DENV in regions experiencing the greatest disease burden. Current serological diagnostics have a limited capacity to distinguish between DENV and ZIKV. On page 823 of this issue, Stettler et al. (2) characterize monoclonal antibodies (mAbs) isolated from ZIKV-infected humans that hold promise as diagnostics or therapeutics, and advance our understanding of the repertoire of antibodies elicited by ZIKV infection.