"Blood type" typically refers to the combination of antigens present on the surface of an individual's red blood cells (RBCs). These antigens are specific sites located on the cell membrane and can be various proteins, glycoproteins, or glycolipids. They serve a range of functions, including acting as membrane transport proteins (e.g., Diego and Kidd), receptors and adhesion molecules (e.g., Duffy and Lutheran), complement regulatory glycoproteins (e.g., Cromer and Knops), enzymes (e.g., Yt, Kell, and Dombrock), structural components (e.g., Diego and Gerbich), or glycocalyx components (e.g., MNS).

Antigens are substances capable of inducing an immune response. When the body encounters foreign antigens, it produces corresponding antibodies, which can be generated through natural or passive immunity. The genetic variations in red blood cell surface antigens determine an individual's blood type.

A blood group system is defined as a system comprising one or more antigens, which are controlled by a single gene or a complex of closely linked homologous genes. Each blood group system is genetically distinct from others. To identify a blood group system and its antigens, it is necessary to recognize and confirm genetic variations that affect the phenotype.

The International Society of Blood Transfusion (ISBT) Blood Group Terminology Working Party (ISBT WP) maintains the official records of all recognized blood group systems. As of November 2023, there are 45 recognized blood group systems containing 362 red blood cell antigens. These 45 blood group systems are determined by 50 genes.