In this review, we give an overview of aspects related to the congenital transmission of the Zika virus (ZIKV). Although we acknowledge that important advances in research on ZIKV pathogenesis have come from studies using animal models, particularly non-human primates, this review emphasizes studies using ex-vivo human cells and tissues as well as natural infections in pregnant women. The possible routes used by ZIKV to cross or breach the placental barrier and infect the fetal central nervous system are presented. Understanding the viral infection biology and ZIKV pathogenesis during pregnancy may guide the design of affordable antiviral strategies to benefit pregnant women in areas at risk.