Over half of HIV infections globally occur among cisgender women. High HIV incidence among young (ie, 15–30 years old) African cisgender women persists during pregnancy and postpartum, and there is evidence that HIV acquisition risk more than doubles during this period. A new HIV infection has important short- and long-term consequences for the mother’s health. Acute maternal HIV infection is also associated with increased vertical transmission risk, making prevention of HIV among pregnant and breastfeeding populations a global health priority. As access to antiretroviral therapy continues to expand, new—and often undiagnosed—maternal HIV infections during pregnancy and breastfeeding contribute to a growing proportion of new pediatric HIV cases, and urgent focus of interventions to eliminate vertical HIV transmission. To address this important gap, The World Health Organization (WHO) and several national HIV programs recommend offering pre-exposure prophylaxis (PrEP) to pregnant and breastfeeding populations at substantial risk for HIV. To fully realize the promise of PrEP in antenatal and postnatal settings, however, “real world” clinical and implementation data are urgently needed. Further, there is a need for research on novel, long-acting tools that prevent HIV acquisition in all populations, including pregnant and breastfeeding populations.