Hemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis, is caused by maternal IgG antibody destruction of the fetal RBCs. Rhesus (Rh) blood group incompatibility (frequently triggered by D antigen) and ABO incompatibility are common causes. In Rh incompatibility, an RhD-negative mother carries an RhD-positive baby; thus, antibodies form against antigens when fetal RBCs cross into the maternal circulation. In ABO incompatibility, commonly, a mother with blood type O has existing antibodies to A and B antigens. The affected baby can suffer from hemolytic anemia leading to severe neonatal jaundice, hydrops fetalis, cardiac complications, and fetal demise. If the pregnancy is affected by Rh incompatibility, antenatal surveillance is done to determine the need for intrauterine transfusion and early delivery. Postnatal treatment includes close monitoring, phototherapy for jaundice, and exchange transfusion in severe cases. For RhD-negative mothers, maternal sensitization can be prevented by using anti-D immunoglobulin (RhoGAM). Prognosis is excellent with prenatal care, blood type screening, and availability of RhD immune globulin.