The red cell membrane consists of a lipid bilayer, a variety of proteins studded therein, and the glycans that stick outward, being linked covalently either to proteins or to lipids. Protein or glycan domains constitute the structural bases of blood groups. Biochemical and molecular studies have led to a definition of the biological functions of molecules expressing blood group antigens. These molecules play a critical role in susceptibility to infections by malarial parasites, some viruses, and bacteria. Diverse inherited and acquired diseases are associated with alteration of red blood cells antigen expression, and these alterations often play a role in the clinical manifestations of these diseases, most of which are haemolytic anaemias of various descriptions. The next study of the functions of blood group antigens will lead to better understanding of the physiological role of these molecules and to the therapy of diseases.