The emerging mosquito-borne virus, Zika virus (ZIKV), has been causally associated with adverse pregnancy and neonatal outcomes, including miscarriage, microcephaly, serious brain abnormalities, and other birth defects indicative of a congenital ZIKV syndrome. In this review, we highlight work from human and animal studies on routes of infection in pregnancy that lead to adverse fetal and neonatal outcomes. A number of innate and adaptive immune mechanisms and signaling molecules that may have key roles in ZIKV infection pathogenesis are discussed along with putative viral entry pathways. A more granular understanding of pathogenesis of ZIKV infection during pregnancy is critical for developing therapeutics and vaccines and mounting a global public health response to limit ZIKV infections. We also report on new therapeutic interventions that have shown success in preclinical studies.