Maternal and neonatal immunization (MNI) is a core component of the new immunization model in the Americas, which transitioned from immunization of children to that of the entire family. Immunization during pregnancy protects the mother and the fetus by providing the neonate with maternal antibodies against disease. It has the potential to impact early childhood morbidity and mortality, and thus MNI has gained visibility and priority on the global health agenda. The Region of the Americas is a leader in MNI, as seen by its elimination of congenital rubella syndrome in 2015 and the progress made toward neonatal tetanus elimination. In the Americas, 31 countries currently target pregnant women for influenza vaccination; and 21 countries—over 90% of the Region's birth cohort—have nationwide newborn hepatitis B vaccination. This paper describes the status of MNI in the Americas and identifies gaps in the evidence, obstacles to optimal implementation, and opportunities for future improvements. Catalysts for MNI in the Region have been political commitment, endorsement by scientific societies, an established “culture of vaccination,” widespread access to antenatal care, and con-text-specific communications; however, universal and equitable access for pregnant women and their newborns continues to be a formidable challenge, and additional vaccine safety and effectiveness evidence is needed. Continued efforts to integrate MNI with maternal and child health services will be critical to furthering the MNI platform as well.