Fetal anemia is defined as the diminished concentration of fetal hemoglobin below two standard deviations for gestational age. In Argentina as well as in most developing countries, this disease is one of the leading causes of fetal-neonatal morbidity and mortality (5% of perinatal deaths) due to the lack of appropriate prophylaxis with postpartum anti-D γ-globulin and inadequate prenatal control. Fetal anemia is originated in the mother due to the presence of specific antibodies–originated In Rhesus factor (Rh)—negative mothers whose husbands are Rh-positive and whose immunization occurred during pregnancy, abortion, postpartum or incompatible transfusions that pass through the placenta agglutinate and hemolyze fetal red blood cells, thus causing fetal anemia and hemolytic disease. In the most severe cases, the fetus can be hydropic or die in utero due to congestive cardiac failure. In our experience, the immunization frequency in Rh-negative patients during their second pregnancy with compatible Rh-positive fetuses is 12–15%. The cornerstone of the follow-up of the sensitized Rh-negative woman is a composite of an appropriate anamnesis, the indirect Coombs test, titration of anti-D antibodies, ultrasound (US) middle cerebral artery (MCA) peak systolic velocity, amniotic fluid spectrophotometry, amniocentesis/cordocentesis, and antenatal fetal monitoring. The pillar of the treatment of severe maternal-fetal Rh-incompatibility to prevent fetal death and allow the fetus to reach viability is intrauterine fetal transfusion (by the intraperitoneal route or intravascular fetal transfusion), high intravenous dose immunoglobulin (HDIVIg) as a single treatment or followed by intrauterine transfusions (IUTs). The neonatal treatment of the newborn is based on phototherapy and HDIVIg, which reduce the frequency of neonatal transfusions needed and the bilirubin maximum levels.