During the course of the twentieth century, at least 270 authenticated alloantigens have been recognised on the red cell surface. Most of these have been classified into 26 blood group systems, each of which represents a single gene or a cluster of two or three closely-linked homologous genes. Most blood group polymorphisms result from single nucleotide changes encoding amino acid substitutions in cell surface proteins. Many other mechanisms, including recombination between homologous genes, are also involved, especially in the complex Rh and MNS systems. There are at least three common molecular backgrounds to the RhD-negative phenotype. Some blood group antigens are carbohydrates, the polymorphisms resulting from mutations within genes encoding glycosyltransferases. Red cell surface proteins perform a variety of functions. For some the functions are well understood, but for most they can only be surmised from the structure of the protein. Putative functions include, membrane transport, cell adhesion, complement inactivation, binding chemokines, and anchoring the plasma membrane to the cytoskeleton. Some erythroid cell surface antigens may serve their primary purpose during erythropoiesis. Analysis of the development of these proteins on erythroid cells during erythropoiesis, ex vivo, has provided clues to their functions and a useful set of markers for the study of erythropoiesis.