The Rh blood group system (including the Rh factor) is one of the currently 30 human blood group systems. It is clinically the most important blood group system after ABO. The Rh blood group system currently consists of 50 defined blood-group antigens, among which the 5 antigens D, C, c, E, and e are the most important ones. The commonly-used terms Rh factor, Rh positive and Rh negative refer to the D antigen only. Besides its role in blood transfusion, the Rh blood group system, in particular the strongest D antigen, is a relevant cause of the hemolytic disease of the newborn for which prevention is key.