Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.“,”Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.