Human blood types are inherited and contain genetic contributions from each parent. Blood types are determined by antigens, which are molecules that trigger immune response on the surface of red blood cells. There are actually vastly more than four blood types — the International Society of Blood Transfusion (ISBT) recognizes 29 different blood group systems, encompassing over 600 distinct antigens. However, the most well known and medically useful blood group system, called ABO, distinguishes four blood types.

ABO blood types are important because blood of a different type than one's own can cause a fatal immune response if introduced into the body. Along with antigens on the red blood cells, the body carries antibodies in the immune system that recognize and fight off the antigens in foreign blood. The ABO system deals with the presence or absence of two specific antigens, called A and B.

Red blood cells can have A or B antigens, or both A and B antigens, or neither. Blood with A antigens alone is classified as type A, while blood with only B antigens is type B. Blood with both A and B antigens is classified as type AB, and blood with neither antigen is type O.

The immune system has antibodies that protect against antigens that are not present in the body's own blood. Those who have type A blood possess Anti-B antibodies; type B blood possesses Anti-A antibodies; AB blood has neither of these antibodies, and people with type O blood have both. Patients cannot receive blood transfusions from donors whose blood contains an antigen that their own blood does not, because their antibodies will launch a defense against it. Ideally, both the donor and recipient in a blood transfusion should have the same blood type. If this is not possible, however, other combinations are safe.

Type O blood is known as the "universal donor." Since it carries neither A nor B antigens, it can exist in the presence of both Anti-A and Anti-B antibodies and is therefore compatible with any recipient blood type. Conversely, Type Os can only receive blood from another type O.

Type AB blood is likewise called the "universal recipient." People with type AB blood have neither Anti-A nor Anti-B antibodies, so they can accept any ABO blood type from a donor. However, those with AB blood can only donate blood to recipients with the same blood type. Blood types A and B are mutually incompatible for blood transfusions, but both can donate to a type AB recipient or receive blood from a type O donor.

The ABO blood group system is often supplemented with the Rhesus blood group system. Though the latter system deals with five specific antigens, it defines only two significant blood types, according to the presence or absence of the D antigen: RhD negative and RhD positive. Those with blood types in the ABO system are sometimes said to be positive or negative, as in "Type O negative," as RhD negative recipients are not compatible with RhD positive donors.