ABSTRACTThe neonatal Fc receptor (FcRn) plays an important role in the transfer of the immunoglobulin G isotype (IgG) from the mother to the fetus. FcRn expressed on endothelial cells also binds to IgG and albumin, regulating the circulating half‐lives of these proteins. Alloimmune and autoimmune IgG antibodies have been implicated in various perinatal immune‐mediated diseases. FcRn‐mediated placental transfer of pathogenic antibodies can result in cell and tissue injury in the fetus and neonate, with devastating outcomes. Thus, blockade of FcRn may be an effective treatment strategy in managing these conditions and could additionally reduce the concentration of pathogenic antibodies in the maternal circulation by preventing IgG recycling. In this review, we discuss the biology of FcRn, the rationale and considerations for development of FcRn‐blocking agents, and their potential clinical applications in various perinatal immune‐mediated diseases. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.