The Rh blood group system is one of the most important human blood group systems, second only to the ABO system. It is primarily determined by the presence or absence of the RhD antigen on the surface of red blood cells. Individuals who have the RhD antigen are Rh-positive (approximately 85% of the population), while those who lack it are Rh-negative. The Rh system is genetically complex, involving two genes, RHD and RHCE, located on chromosome 1.

The clinical significance of the Rh blood group lies mainly in its role in Rh incompatibility, particularly during pregnancy. If an Rh-negative mother carries an Rh-positive fetus, her immune system can become sensitized to the fetal RhD antigen, typically during delivery or if fetal blood enters her circulation. In subsequent pregnancies with an Rh-positive fetus, the mother's antibodies can cross the placenta and attack the fetal red blood cells, leading to hemolytic disease of the newborn (HDN), which can cause severe anemia, jaundice, and even death in the fetus or newborn. This condition is largely preventable today through the administration of Rh immunoglobulin (RhoGAM) to Rh-negative mothers at specific times during pregnancy and after delivery, which prevents the mother's immune system from producing anti-RhD antibodies. Understanding the Rh blood group is crucial for safe blood transfusions and preventing HDN.