The explosive emergence of Zika virus has inspired a global effort to develop vaccines. Zika virus, which is a flavivirus primarily transmitted by mosquitoes, can cause devastating congenital syndrome in fetuses of pregnant women, including microcephaly, craniofacial disproportion, spasticity, ocular abnormalities, and miscarriage. In adults, Zika infection has been linked to the autoimmune disorder Guillain-Barré syndrome. Thus, despite the current waning in newly reported Zika infections, an efficacious vaccine is urgently needed to help limit the emergence of another detrimental epidemic. Here we summarize the current status of the Zika vaccine pipeline and highlight the challenges for clinical efficacy trials.