Hemolytic disease of the fetus and newborn (HDFN) is a condition marked by the destruction of fetal red blood cells due to maternal antibodies that cross the placenta. Maternal antibodies form due to a sensitizing event, typically a prior pregnancy, during which the maternal immune system is exposed to incompatible fetal red blood cell antigens. The most widely recognized cause is RhD antigen incompatibility, although there are many other clinically significant red blood cell antigens. Pregnancies affected by alloimmunization are at risk for complications including fetal anemia, hydrops fetalis and fetal death. These pregnancies, therefore, require frequent monitoring and sometimes invasive interventions, such as fetal blood transfusions in utero, to improve pregnancy outcomes.