Abstract The Kell and Kx blood group systems are expressed as covalently linked molecules on red blood cells (RBCs). The Kell blood group system is very polymorphic, with 35 antigens assigned to the system. The expression of Kell glycoprotein on RBCs is not critical to the erythrocyte function. However, the expression of Kx is critical to normal morphology, and null mutations are associated with the McLeod neuroacanthocytosis syndrome. The immunogenicity of the K antigen is second only to the D antigen, and alloantibodies to Kell antigens can cause transfusion reactions and hemolytic disease of the fetus and newborn. Kell alloantibodies in pregnancy are known to suppress erythropoiesis, which can result in serious disease despite low amniotic bilirubin levels and low antibody titers. Late-onset anemia with reticulocytopenia is thought to be attributable to the continual suppression of erythropoiesis from residual alloantibody in the infant. Alloimmunization to XK protein is rare, and expressed polymorphisms have not been reported. Together these two blood group systems share an integral relationship in transfusion medicine, neurology, and musculoskeletal biology. Immunohematology 2015;31:14–19.