Vertical transmission, or mother-to-child transmission (MTCT), is the main mode of HIV-1 acquisition in infants and children. The presence of passively transferred maternal antibodies to HIV-1 has not protected infants front HIV-1 infection and there is no clear understanding about the role of antibodies in preventing MTCT. Immune factors, such as leukemia inhibitory factor, CC chemokines, Lewis X component and secretory leukocyte protease inhibitor, appear to be involved in the protection of HIV-exposed, uninfected infants. The mainstay of reducing HIV transmission risk in infants remains the use of antiretroviral therapy. Future strategies to augment the role of antiretrovirals in preventing MTCT, or to target the prevention of transmission through breastfeeding, may include the use of vaccination and/or passive immunization with neutralizing monoclonal antibodies.