Widespread availability of antiretroviral therapy among pregnant women living with HIV has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV across the globe. However, while Joint United Nations Programme on HIV/AIDS has set targets to reduce the annual number of new pediatric HIV infections to fewer than 40,000 in 2018 and fewer than 20,000 in 2020, progress towards these targets has plateaued at an unacceptably high global estimate of greater than 160,000 children newly infected with HIV in 2018. Moreover, it has become clear that expansion of maternal antiretroviral therapy alone will not be sufficient to close the remaining gap and eliminate MTCT of HIV. Additional strategies such as maternal or infant passive and/or active immunization that synergize with maternal antiretroviral therapy will be required to end the pediatric HIV epidemic. In this review, we outline the landscape of existing maternal interventions and emerging maternal immune-based approaches to prevent MTCT of HIV.