Publisher Summary This chapter discusses the serological testing of donated blood. The donated blood need to be tested for its ABO and D-antigen status for preventing ABO-incompatible blood transfusions and D-antigen sensitization. RBC products often undergo further RBC antigen characterization for supplying blood products for patients with alloantibodies or patients with chronic anemia who require phenotypically-similar RBC components. The serologic methods used by blood centers to perform these tests include tube testing, gel method or solid phase testing. The ABO blood group phenotypes include A, B, AB and O and reciprocal antibodies are present in sera of majority of individuals and so it can result in severe intravascular hemolysis after transfusion of ABO-incompatible blood components. The D-antigen is the most immunogenic of the RBC antigens and donor centers must ensure that D-negative products are appropriately labeled to prevent D-negative product forming anti-D in response to transfused RBCs in the recipient. The other serologic methods discussed include antibody screening for the presence of unexpected RBC antibodies, phenotyping of RBC products and antibody titer anti-A, Anti-B.